Human microbiology Flashcards
What is microbiome?
The microbiome is the community of microorganisms (fungi, bacteria, virus, etc.) that exists in a particular environment.
What are general components of a microbiome?
Microbiota are microorganisms belonging to different kingdoms, including bacteria, archaea, protozoa, fungi, algae, and viruses.
Structural elements (“theatre of activity”) are the microbial structures, metabolites, mobile genetic elements, etc.., as well as proteins/peptides, lipids, polysaccharides, nucleic acids (structural DNA/RNA).
Environmental conditions of the habitat (biome = a reasonably well defined habitat which has distinct bio-physio-chemical properties), including the environmental conditions, nucleic acids (mobile genetic elements, virus/phages relic DNA, microbial metabolites (signalling molecules, toxins, (an)organic molecules.
The microbiome forms a dynamic and interactive micro-ecosystem prone to change in time and scale, and it is integrated in macro-ecosystems including eukaryotic hosts, and crucial for their functioning and health.
What are the differences between gut and skin microbiome?
1: environmental conditions:
* The gut provides a moist, nutrient-rich environment with a relatively stable temperature, which is mostly anaerobic (low O2). The pH varies along different parts of the GI tract, influencing microbial composition.
* The skin is exposed to the external environment, making it a more variable and often harsher habitat. It is generally cooler and drier than the gut and is exposed to O2. the skin’s pH is typically acidic, which helps in inhibiting the growth of pathogenic bacteria.
2: microbial composition
* Gut: dominated by bacteria (particularly from the phyla Firmicutes and Bacteroidetes + the Actinobacteria and Proteobacteria). It also contains archaea, fungi, viruses, and protozoa.
* Skin: is more diverse in terms of species composition (higher heterogeneity). It is primarily colonized by bacteria from the phyla Actinobacteria, Firmicutes (Staphylococcus), Bacteroidetes, and Proteobacteria. Fungi (Malassezia) and viruses also form significant parts of the skin microbiome.
3: functions
* Gut: plays a crucial role in digestion and metabolism, aiding in the breakdown of complex carbohydrates, synthesis of vitamins (vitamin K, and some B vitamins), and absorption of minerals. It has a high significant impact on the immune system helping in development of immune tolerance and protection against pathogens. And, influences systemic health impacting conditions; like obesity, diabetes, and inflammatory bowel disease.
* Skin: protect against pathogens by competing for nutrients and space, producing antimicrobial peptides (AMPs), and contributing to the skin’s immune defence. It helps in wound healing and modulates the local immune response. And, influences skin conditions like acne, eczema, and psoriasis.
4: stability and resilience
* Gut: generally more stable over time if not perturbed by factors like antibiotics, drastic dietary changes, or illness. Changes in the gut microbiome can have a profound effects on overall health due to its systemic connections.
Skin: more susceptible to changes due to external factors such as hygiene particles, cosmetics, humidity, and exposure to environmental microbes. While changes can affect local skin health, systemic effects are less common.
Describe which methods can be used for studying the microbiome?
Microbiome composition:
16S rRNA gene sequencing look at the bacterial and archaeal communities.
* Method: amplification of the 16S ribosomal RNA gene, a highly conserved region with variable regions that provide species-specific signatures.
* Output: phylogenetic information that can be used to infer community composition.
Microbiome function:
Metabolomics looking at metabolites produced by the microbiome
* Method: use techniques like MS or NMR spectrometry to identify small molecules
* Output: profiles of the metabolites present, which can be used to infer microbial functions and interactions with the host.
Metagenomic shotgun sequencing looks at the functional potential of the microbiome
* Method: high-throughput sequencing of the collective genomes (metagenome) of the microbiome with a focus on the functional annotation of genes.
Output: a catalogue of genes present in the microbiome and their potential functions in high resolution.
What is gamma, beta, alpha diversity, species richness, and evenness?
Alpha diversity = measure diversity within sample. It is usually expressed by the number of species (species richness) and evenness (equitability) in the sample. The Shannon index combine the richness with the evenness. There are some limitations including that it cannot discriminate between the bacteria species, and only the numbers of species.
Beta diversity = measure dissimilarity between samples. It is the ration between the species and a comparison of species diversity between environments and is often used to indicate the extent of species turnover or replacement along environmental gradients or between habitats. It is used in several indexes: Jaccard index (fraction of taxa between samples), Bray-Curtis index (takes abundance into account), and UniFrac (incorporates phylogenetic distances)
Gamma diversity = measure of the overall diversity. It takes into account the total number of species observed in all ecosystems when considered together.
Species richness = number or organisms present in the sample. It is the number of microorganisms that you are measuring.
Evenness = relative abundance of different organisms. It takes into consideration how equal the populations of each species are within a sample.
What is the difference between 16S rRNA and metagenome sequencing?
16S rRNA sequencing specifically targets and sequences the 16S ribosomal RNA gene to identify and classify bacteria present in a sample, whereas metagenome sequencing involves sequencing all the genetic material in a sample, providing a comprehensive overview of all microorganisms, including bacteria, viruses, fungi, and archaea + their functional potential.
Which methods can say which microbes are present and which can describe what are the microbes doing? (What methods are used to describe microbiome composition and function?)
The methods that can say which microbes are present are the metagenomic sequencing and the 16S rRNA sequencing.
The methods that can say what the microbes are doing are the metabolomics, proteomics, and metagenomic shotgun sequencing.
Which animal models used in microbiome do you know?
Animals: mouse (germ-free or wild-type), fly (drosophila), zebrafish (C. elegans).
Explain how the gut microbiome is important for the normal functioning of the host organism (list at least 5 main functions)
1: metabolism
2: immune system functioning
3: digestion
4: syntehsis of essential vitamines (ex: Vitamin K and some B vitamines).
5: gut-brain axis; some diseases like depression is linked to the microboime composition.
What is a major route for establishing the gut microbiome in newborns?
Vertical transmission from mother to child.
1: During birth: vaginal delivery - the newborn’s gut is colonized by microbes from the mother’s vaginal and faecal microbiota. This is considered a critical moment for the initial establishment of the gut microbiome. Ex: Home-birth vs home birth c-section
2: Postnatal factors: Breastfeeding - breast milk contains beneficial bacteria and oligosaccharides that promote the growth of specific microbial populations in the infant gut - phylobacteria very important in training the gut bacteria!
3: Skin-to-skin contact - direct skin contact with the mother and other family members also contributes to the colonization of the newborn’s skin and gut microbiota. Ex: Family members and animals.
Which factors influence the resilience of the microbiota?
1: Resilience - the species richness
2: External interventions: prenatal factors (placenta, and maternal diet/exercise/lifestyle), neonatal factors (mode of delivery, and gestational age), and postnatal factors (feeding: breastmilk vs. formula, geographical location, family members, host interactions, maternal diet, and weaning)
Which life stages have low stability of the gut microbiome?
The age with low stability of the gut microbiome; Infancy, Early childhood, childhood, adolescence, and during the age of retirement.
Low stability is connected to the resilience of microbiome. Low stability = low resilience.
What mechanisms are used by the human host to control gut microbiota composition?
The main mechanisms involves:
1: biochemical barriers - pH and bile acids (the acidic environment of the stomach and the presence of bile acids in the intestine can inhibit or kill certain bacteria, influencing the composition of the microbiota), and nutrient availability (the host regulates the availability of nutrients, which can selectively feed or starve certain microbial populations).
2: physical barriers - mucus layer (the gut epithelium is coated with a mucus layer that serves as a physical barrier, preventing direct contact between bacteria and host cells), and epithelial cell turnover (regular shedding of intestinal epithelial cells helps remove adherent bacteria, contributing to the control of the gut microbiota composition.
3: gut mobility - peristalsis (regular movement of the gut helps in the clearance of microbes and prevents overgrowth.
4: intracellular communication - microbiota host signalling (host cells and microbiota communicate through signalling molecules (short-chain fatty acids (SCFAs), which can influence immune responses and epithelial integrity).
5: diet and lifestyle - dietary compensation (dietary fibers, polyphenols, and other nutrients can selectively promote the growth of beneficial microbes), and lifestyle choices (factors like stress, sleep, and exercise can indirectly affect the gut microbiota through changes in host physiology and immune function).
How do gut microbes contribute to human metabolism?
The main mechanisms involves:
1: digestion and nutrient absorption - breakdown of complex carbohydrates (many gut bacteria can ferment indigestible dietary fibers, breaking them down into absorbable nutrients), and production of short-chain fatty acids (SCFAs) (the fermentation process produces SCFAs like butyrate, propionate, and acetate, which sever as energy sources for colonocytes and have systemic metabolic effects.
2: synthesis of vitamins and amino acids - vitamin production (gut microbes synthesize essential vitamins (vitamin K and certain B vitamins) including folate and biotin, which are crucial for human health), and amino acid metabolism (some gut bacteria can produce amino acids and modulate their levels, impacting protein metabolism).
3: modulation of metabolic pathways - influence on lipid metabolism (SCFAs and other microbial metabolites can influence lipid metabolism, affecting cholesterol levels and the risk of cardiovascular disease), and impact on glucose homeostasis (gut microbiota can affect glucose metabolism by modulating host insulin sensitivity and energy expenditure).
4: detoxification - modification of xenobiotics (gut bacteria can modify drugs and other xenobiotics, affecting their bioavailability and toxicity).
5: gut-brain axis - neuroactive compounds (some gut bacteria can produce/modulate neuroactive compounds (serotonin and GABA), influencing host behavior and appetite regulation.
6: hormonal regulation - modulation of hormone levels (gut microbiota can influence the levels of hormones involved in metabolism (ghrelin, leptin) affecting hunger and satiety signals)
Why is it interesting to study the microbiome?
