MHD7 Gut microbiota and aging Flashcards

1
Q

How many different types of species are there in a human faeces sample?

A

Roughly 160

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2
Q

When is the host microbiome most malleable?

A

in early life and in late life

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3
Q

Is the gut of the foetus sterile before birth?

A

The gastrointestinal tract has long been thought to be sterile at birth with bacterial colonisation beginning during the delivery process (from the maternal faecal or vaginal microbiota and/or the environment). However, researchers have found evidence of bacteria in the placenta, amniotic fluid and meconium (first stool that forms in a foetus in utero).
Other scientists argue that this is due to contamination

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4
Q

Define kitome

A

Contaminants from the DNA-extraction kits.

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5
Q

What is the difficulty when testing placental samples for microbial signal?

A

Placental microbial signal is likely to be weak and difficult to distinguish from the background microbial signal.

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6
Q

During which period is inter-individual variation in the microbiota reduced?

A

Two to three years after birth the human gut undergoes a rapid and dynamic period of colonisation. Bacterial diversity increases.

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7
Q

Which community-type will the gut microbiota of a vaginally-delivered baby resemble at birth?

A

Vaginal

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8
Q

Which community-type will the baby’s gut microbiota resemble at 27 months?

A

Feacal

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9
Q

What are the two significant transitions that the establishment of a stable gut microbiota generally accompany? Explain these

A

1) The first transition occurs soon after birth during lactation. Initial bacteria to colonise the large gut are facultatively anaerobic strains such as Escherichia coli and streptococci. These first colonisers metabolise any traces of oxygen in the gut reducing the environment into one of strong anaerobic conditions. Once this anaerobic environment is created a range of selection pressures shape the colonisation trajectory of the gut.
2) The second transition occurs during the weaning period, with the introduction of solid foods and continuation of breast milk feeding. Following this transition an adult-type complex microbiome takes shape dominated by the phyla Bacteroidetes and Firmicutes.

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10
Q

What is the early-life microbiota of infants born vaginally dominated by?

A

Lactobacillus, Prevotella, or Sneathia

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11
Q

Infants born by caesarean section have an intestinal microbiota more consistent with what?

A

the skin microbiota. This is dominated by Staphylococcus, Corynebacterium, and Propionibacterium. Environmental factors (e.g. air, healthcare workers, delivery and surgical equipment) also appear to have a greater effect on the microbiota of infants born by caesarean section.

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12
Q

What does caesarean birth have an associated increased risk of?

A

Immune disorders such as allergic rhinitis, asthma, and celiac disease

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13
Q

How do Human milk oligosaccharides (HMOs) reach the colon?

A

HMOs are a major component of breast milk and include oligosaccharides such as galactooligosaccharide (GOS). These HMOs are only partially degraded in the small intestine and so reach the colon

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14
Q

What effect do HMOs have on the colon?

A

They have a probiotic effect, selectively stimulating the development of a Bifidobacterium-rich microbiota (referred to as “Bifidus flora”).

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15
Q

How are HMO broken down in babies?

A

The bifidobacteria ferment these oligosaccharides to produce short chain fatty acids.

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16
Q

What is the difference in gut microbiota of infants fed on breast milk versus formula milk?

A

Formula-fed infants develop a complex microbiota with higher proportions of facultative anaerobes, such as Bacteroides and Clostridia, than breast-fed infants who are colonised more commonly by aerobic organisms. Breast milk also contains numerous factors that modulate and promote the maturation of the immune system, which in turn can select the bacteria that colonise the gut. The faecal microbiota of breast-fed infants exhibits more dramatic changes in composition over their first year of life. Breast milk has also been found to contain members of the Lactobacillus, Streptococcus, Enterococcus, Peptostreptococcus, Staphylococcus, Corynebacterium, and Escherichia species

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17
Q

The use of antibiotics is ____ prevalent in pre-term and caesarean babies

A

more

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18
Q

In infants, antibiotic exposure shifts the gut microbiota towards a high abundance of what types of bacteria? What other impact does it have on the microbiota?

A

Proteobacteria and low abundance of Actinobacteria populations.
It also reduces the overall diversity of the infant microbiota and selects for drug-resistant bacteria.

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19
Q

Exposure to broad-spectrum antibiotics for the first four days of life has been shown to do what to the infant’s microbiota?

A

Reduce colonisation by Bifidobacterium and increase colonisation by Enterococcus. In these infants, an overgrowth of Enterobacteriaceae and Enterococcus was seen by one month of life.

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20
Q

Epidemiological studies have found an association between early-life antibiotic intake and an increased risk for what diseases?

A

type 1 diabetes, asthma, atopic disease and eczema

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21
Q

What other factors are proposed to affect the early-life development of the microbiota?

A
Host genetics
Composition of the maternal microbiome
Length of gestation
Birth environment
Hygienic practices
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22
Q

What are the main factors that influence childhood gut microbiota?

A

geography and dietary habits

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23
Q

What is the basic difference between the gut microbiota of children vs infants?

A

The microbiome of children is more stable than that of the infant and has less variability across individuals.

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24
Q

What is the difference in faecal microbiome of children from USA vs Bangladesh?

A

Bangladeshi children were found to have higher bacterial diversity and possess communities dominated by Prevotella. In contrast, the US children had less diversity and a community dominated by Bacteroides and Firmicutes.

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25
Q

What is the difference in faecal microbiota between children from central Asia and South East Asia vs children from Eastern Asia?
What may be part of the reason for this?

A

Central Asia and South East Asia: Prevotella-dominated (P-type) microbiota
Eastern Asia: Bacteroides-Bifidobacterium-dominant (BB-type) microbiota
Diet

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26
Q

What is the difference in faecal microbiota between rural and urban populations?

A

Rural: P-type microbiota
Urban: BB-type microbiota

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27
Q

What may be the reason for the different P-type/BB-type microbiota?

A

Modernisation of the foods was associated with these differences with the urban children (BB-type) consuming a high-fat diet compared to those from the rural setting (P-type). The BB-type microbiome was enriched with genes encoding bile acids that aid in lipid absorption and the P-type microbiome was enriched for genes involved in oligosaccharide-degrading enzymes involved in plant digestion.

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28
Q

Is genome or diet a greater influence on gut microbiome?

A

Interestingly, most children enrolled on the study were Filipino and the two sites were only 50 km apart showing that the influence of the diet on shaping the microbiota was greater than the influence of the genome.

29
Q

What is the pre-weaning gut microbiota like?

A

Enriched with genes that facilitate lactate utilisation

30
Q

What is the post-weaning gut microbiota like?

A

Capacity to utilise a wide range of carbohydrates, vitamin biosynthesis and xenobiotic degradation

31
Q

What is the adult gut microbiota like?

A

Stable microbiome dominated by carbohydrate metabolism genes

32
Q

When is the peak numbers and diversity in gut microbial composition is reached?

A

Near the end of adolescence

33
Q

What has made it difficult to define “normality” of gut microbiota in adults?

A

The high amount of inter-individual variation in the intestinal microbiota across adults

34
Q

What are the most abundant phyla in the adult colon (making up ~95% of the microbiota)?

A

Firmicutes and Bacteroidetes The next most abundant phylum is the Actinobacteria (mainly comprised of the genus Bifidobacterium) and Proteobacteria

35
Q

Following Firmicutes and Bacteriodetes, what is the next most abundant phylum?

A

The Actinobacteria (mainly comprised of the genus Bifidobacterium) and Proteobacteria

36
Q

Once an individual’s colonic microbiota has reached its climax community, what happens?

A

it appears to be relatively stable throughout adulthood

37
Q

Why would there be pronounced shifts in the adult microbiome?
How can these be reverted?

A

due to lifestyle changes of the host or following exposures such as sudden dietary alterations, the acquisition of a pathogen, or antibiotic exposure.
However, when such pressures are removed the microbiome typically recovers close to its original state

38
Q

Small intestine has been found to contain mainly what bacteria?

A

Streptococci and bacteria belonging to the genera Clostridium and Veillonella

39
Q

What is a trait of small intestine microbiota not observed in the colonic microbiota? Why does this variation occur?

A

Temporal fluctuations were observed in the small intestinal microbiota, with the composition differing throughout the day. This is likely to reflect exposure to a variety of dietary components and host secretions.

40
Q

Antibiotic exposure is associated with a _______ in Actinobacteria and a ______ in Proteobacteria

A

decrease

increase

41
Q

Bifidobacteria belong to which bacterial phylum?

A

Actinobacteria

42
Q

Above the age of 60-65 what change occurs to the microbiome?

A
  • large decrease in the abundance of the gut microbial probiotics, bifidobacteria and lactobacilli
  • decrease in the relative abundance of Firmicutes including Ruminococcus and Blautia species that produce butyrate
  • increase in the proportion of Bacteroidetes and Escherichia species
43
Q

Why are there changes in the gut microbiota of individuals over time?

A

Inflammation and reduced energy availability within the gut. The loss of beneficial bifidobacteria, both in terms of abundance and species diversity, is one of the most pronounced changes in the ageing gut. In the community setting, microbial shifts are small and correlate with age, but when individuals enter long-term residential care settings these microbial shifts become more pronounced.

44
Q

Why is there increased faecal impaction and constipation in elderly individuals?

A

Intestinal motility and transit time are slower in older people

45
Q

What can elevated retention time present in elderly people cause?

A

An increase in detrimental metabolites of proteolytic bacteria, such as ammonia and amines. These factors can impact on the composition of the gut microbiota.

46
Q

Why are the diets of elderly individuals more limited than those of adults? What does this lead to?

A
  • immune dysfunction: reduces the ability of the host to maintain the commensal microbiota structure and function and allows pathobionts and pathogenic bacteria to proliferate.
  • high sugar and high fat foods with less carbohydrates and fewer nutrients.
  • > This may be a result of higher thresholds for taste and smell than younger adults and loss of tooth function with difficulties in chewing and swallowing.
  • —> Lower fibre intake leads to a decrease in microbiota diversity.
47
Q

In elderly individuals what does their lower diversity in the microbiota lead to/influence?

A
  • may influence food cravings.

- the loss of diversity in the core microbiota groups has been associated with frailty and reduced cognitive performance

48
Q

What is immunosenescence? Describe in detail

A

Age-related immune dysfunction: This is the gradual deterioration of the immune system and can result in elderly populations having reduced immune defences to exogenous infectious agents and may increase immune responses to endogenous signals. Increased levels of cytokines, such as interleukin-6 (IL-6), IL-1β, and tumour necrosis factor-α (TNF-α), decreased phagocytosis and natural killer (NK) cell activity have been observed in elderly populations.

49
Q

Other factors that may modify the microbiome with ageing include:

A
  • Changes in bacterial receptor (attachment) sites in the gut itself
  • Lesser mobility
  • Recurrent infections
  • Hospitalisations
  • Use of medications
50
Q

Individuals with a high frailty score had a significant reduction and increase in the proportion of what bacteria?

A

Decrease: Bacteroides/Prevotella, lactobacilli and Faecalibacterium prausnitzii
Increase: Atopobium, Enterobacteriaceae, and Ruminococcus

51
Q

The combination of immunosenescence and microbial alterations could lead to what?

A

irreversible host dysfunctions driving the rapid deterioration of health and increase the risk for age-associated pathologies and ultimately death

52
Q

The gut microbes can compete with the ________ for nutrients in space and can also regulate secretion of mucins, _____ production and also regulate the integrity of the gut barrier, by producing ____

A

pathobionts
AMP
SCFAs

53
Q

What do SCFAs do to tight junctions?

A

enhancing them preventing microbes and metabolites from moving between the cells - something referred to as paracellular absorption: instead these metabolites and microbes have to pass through the cells, this allows the enterocytes to have much greater control over what passes from the luminal environment into the cells and into the circulation.

54
Q

What do dendritic cells induce the activation and differentiation of?

A

Naïve B cells to form plasma cells that produce commensal-specific IgA in the lamina propria.

55
Q

What is a pathobiont?

A

Disease causing organism

56
Q

What happens to IgA produced in the lamina propria?

What does it go on to do?

A

It is transported into the gut lumen and secreted as IgA (sLgA). In the gut, sIgA binds to commensal microbes and soluble antigens, restraining their adherence to the host epithelium and leakage through the gut barrier.

57
Q

in the senescent intestine, what happens?

A
  • A dysbiotic gut microbiota can develop with an overgrowth of pathobionts
  • There is also a thinning of the mucus layer. Removing a further barrier against microbial invasion
  • there is a weakening of tight junction proteins and a loss of intestinal barrier integrity, often referred to as a leaky gut
58
Q

The altered microbiota composition and weakened or perturbed gut permeability may lead to increased what?

A

Adherence and leakage of various microbes and microbial by-products through the gut barrier thereby instigating a hyper-inflammatory response eventually increasing host susceptibility to various gut related as well as systemic disorders

59
Q

What is inflammaging?

A

Chronic low-grade inflammation is seen with ageing

60
Q

Are gut microbial alterations a cause or consequence of inflammation?

A

A study demonstrated that transferring the microbiota from old conventional mice into young germ-free mice, resulted in inflammaging. The same effect was not seen when transferring the microbiota of young conventional mice.

61
Q

This inflammation was associated with increased levels of what?

A

Proteobacteria and TM7 bacteria and lower levels of Akkermansia in the aged microbiota.

62
Q

Why is the ageing population are more prone to infections than any other age group?

A

The age-dependent loss of bifidobacteria and lactobacilli probiotics coincides with an increased susceptibility to such infections with age. This trend appears to occur in both Western and Eastern populations

63
Q

What are bifidobacteria and lactobacilli are known to inhibit?

A

Foodborne pathogens such as campylobacter, listeria, E. coli and salmonella.

64
Q

Prebiotics and probiotics have been shown to do what to elderly? What does this lead to?

A

modulate the gut microbial composition towards a potentially healthier community structure and can also improve their immune function

65
Q

Impaired mucin production in the aged colon allows what?

A

It may increase gut barrier permeability: allowing bacteria in the gut to more easily move across the gut epithelium cells.

66
Q

What does disruption of the mucosal barrier function and changes in the gut microbiota with age increase?

A

The translocation of pathogens from the gut and increase an individual’s susceptibility to infection. Consequently, these events will lead to immune dysregulation

67
Q

The three-way interaction between impaired gastrointestinal tract, imbalanced gut microbiota and inflammation has been associated with what?

A

Increased disease risk in elderly populations, such as infections, inflammatory bowel disease (IBD) and colorectal cancer.

68
Q

Which metabolites increase in the gut with slower intestinal motility?

A

Ammonia and amines