Microbiota in health and disease

15 important questions on Microbiota in health and disease

Why is protein fermentation often considered to have a negative impact on our colonic tissue?

The fermentation of proteins will result in the production of branched SCFA, but also in hazardous components, such as ammonia and sulfide, amines and phenolic compounds.

What common features can be said about newborn babies with respect to the microbiotal composition?

The first microbes are already entering after the first cry through contact wit hthe mother and their environment. The first microbes are facultative anaerobes which convert the oxic environment present in the GI tract into a strictly anoxic environment.
Immediately afterwards, strict anaerobes start to colonize, bifidobacteria are in general dominantly present.
After weaning, the numbers of bifidobacteria decline and the microbiota function seems to become less chaotic.

Is microbiota similar in time/individuals?

Relatively stable in time, but very host-specific. Probably genetic factors play a role, but also environment.
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Explain "Dollo's law of irreversibility".

An organism cannot return to a previous stage that has already been realized in the rank of its ancestors, indicating that once a common ancestor has lost methane production in the intestine, it will not reappear in descendants.

Why seems enterotypes like a feasible hypothesis?

It supports the diagnostics for diseases associated with the GI tract microbiota. Enterotype 3 is very prominent in IBS. Further research needs to be done.

What was the result when they compared conventional mice with germ-free mice in relation to obesity?

Conventional mice have higher body fat percentage, lower calory intake, higher metabolis rate compared to germ free mice. The obese phenotype/microbiota are transferable to germ-free mice.

What is the difference in Bacteriodetes/Firmicutes ratio between lean and obese mice?

Obese mice have higher Firmicutes and less Bacteroidetes compared to lean mice.

What are the proposed mechanisms of the impact of microbiota on obesity?

1. Suppression of fasting-induced adipose factor -> triglyceride accumulation in adipocytes.

2. Inactivation AMP activated protein kinase -> suppression FAO.

3. Signalling microbiota -> promoting low grade pro-inflammatory state.

4. Production SCFA -> energy fuel and regulating transit time and bowel movement via G-protein receptors and enteroendocrine peptide YY.

Please explain the link between obesity and insulin sensitivity.

See lecture 2.1, slide 60.

What are the three subtypes of IBS?

IBS-D: Diarrhea predominant
IBS-C: Constipation predominant
IBS-N: Mixed defecation (most common)

What did O'Mahony and colleagues demonstrated? And Kajander et al?

That a Bifidobacterium infantis-based probiotic resulted in a significant reduction of IBS symptom scores.
It is thought that this strain modulated the immune response in IBS parients by normalizing cytokine IL10/IL12 ratio, which was found abnormal in IBS population.

Kajander found that an intervention with multispecies probiotic significantly decreased IBS symptoms. Micorbiota composition was stabilized.

There is no uniform correlation between microbiota and IBS in different studies. Name 6 possible explanations.

1. IBS is a heterogenous disorder.
2. Number of subjects per study is limited.
3. Single snaphop of microbiota vs chronic characteristic IBS -> more samples in time are needed.
4. Improvement subtyping of IBS patients needed.
5. Enterotype-specific impact?
6. Microbiota analytic tools are different.

How can C. difficile be harmful and what treatment has a high succesrate?

It can be harmful when it increases in number, low levels are not harmful. Transplantation of the microbiota has a high success rate.

Name a model for the impact of bacteria.

See lecture 2.1, slide 79

What are some common features of microbiota in health and disease?

- Multifactorial, etiology unclear.
- Composition microbiota often reduced in diversity and unstable in disease.
- Composition microbiota different in structure compared to healthy individuals.
- Difficult to assign specific microbes to disease.
1. studies have different contradicting observations.
2. in case of correlation; microbe cause or consequence of disease?
3. confounders (use medication etc)
- Microbiota transplantation outcome?

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