Lecture 10: Microbiome and cardiometabolic health

What is the main driver of altered cardio-metabolic risk mediators (insulin resistance, T2DM, HTN, etc.)

high risk obesity

The western diet increases the breakdown of proteins which is called

proteolysis

What detrimental metabolites are increased in the western diet?

ImP, BCAA

What is ImP

imidazole propionate

What produces ImP

breakdown of histidine

Increased ImP and BCAAs are associated with

- increased intestinal permeability

- insulin resistance

- inflammation

A diet rich in fiber increases the fermentation of complex carbohydrates which is called

saccharolysis

Which species is inversely associated with atherosclerosis?

a. P. copri

b. P. gingivalis

c. L. rhamnosus

d. F. praunsnitzii

c

Which species are associated with atherosclerotic cardiovascular disease (ACVD)? (choose all that apply)

a. E. coli

b. K. pneumoniae

c. A. muciniphila

d. K. aerogenes

a, b, d

What bacteria-derived endotoxins does a high-fat diet induce (because of a disrupted intestinal barrier)? (3)

- these endotoxins can enter the portal and systemic circulation

- Lipopolysaccharides (LPS)

- Trimethylamine N-oxide (TMAO)

- imidazole propionate (ImP)

Uremic toxins like p-cresol sulfate and indoxyl sulfate cause

- tight junction breakdown

- systemic inflammation

Secondary bile acids like TGR5 release

GLP-1

SCFA increase

- leptin

- GLP-1

LPS like TLR2, 4 or 9 can cause

- endothelial cell damage

- foam cell formation

- vascular inflammation

- insulin resistance

PAG adrenergic receptors lead to

atherosclerosis & thrombosis

p- Cresol SO4 and Indoxyl SO4 lead to

renal dysfunction

renal fibrosis

TGR5, FXR, and LXR (bile acids) lead to

modulation of lipid metabolism

glucose/insulin metabolism

inflammation

LPS (TLR 2,49) lead to

inflammation

modulation of immunity

Dietary precursors, such as choline and carnitine are metabolized into trimethylamine (TMA) but gut microbiota via specific genes, including members of the

cut (choline utilization) gene cluster C/D

FMOs

flavin monooxygenases (hepatic FMOS)

- oxidize TMA into TMAO

CAD patients had increased levels of:

a. roseburia

b. firmicutes

c. streptococcus

d. Enterococcus

b, c, d

Atherosclerosis patients have increased

a. TMAO

b. lactobacillus

c. roseburia

d. dietary choline and carnitine

a, b, d

A fiber-rich diet increases saccharolysis and beneficial metabolites such as:

a. secondary bile acids

b. ImP

c. BCAA

d. SCFA

a, d

Which species has an association with atherosclerosis?

a. B. vulgatus

b. P. copri

c. P. gingivalis

d. L. plantarum

c

Which genus is associated with lower cholesterol?

a. Bifidobacterium

b. Bacteroides

c. Prevotella

d. Porphyromonas

a

Which two genus are inversely associated with coronary artery disease (CAD)?

a. Bifidobacterium

b. Bacteroides

c. Prevotella

d. Porphyromonas

b, c

Which two species are associated with insulin resistance?

a. B. vulgatus (bacteroides)

b. P. copri (prevotella)

c. P. gingivalis (porphyromonas)

d. L. plantarum (lactobacillus)

a, b

Which species is associated with lowered cholesterol, lower TGs, lower TMAO, and is inversely associated with atherosclerotic lesions?

a. E. coli

b. L. plantarum

c. K. aerogenes

d. K. pneumoniae

b

Which species are all inversely associated with atherosclerosis and atherosclerotic lesions?

a. L. plantarum (lactobacillus)

b. E. coli (escherichia)

c. L. rhamnosus (lactobacillus)

d. R. intestinalis (roseburia)

e. A. muciniphila (akkermansia)

f. P. gingivalis (porphyromonas)

a, c, d, e

Is LPS gram-positive or gram-negative?

gram negative

What cardio-metabolic diseases do endotoxins like LPS induce?

a. insulin resistance

b. hepatic failure

c. type 2 diabetes

d. atherosclerosis

e. thrombosis

a, c, d, e

Dietary __________________ is converted by the gut microbiota into __________________________, which is associated with host diseases such as CVD or CKD.

a. fat; TMAO

b. phosphatidylcholine; TMAO

c. phosphatidylcholine; TGs

b

What can TMAO cause

- atherosclerosis

- renal impairment

What converts TMA into TMAO? what organ is it found in?

a. FMO3; kidney

b. LPS; liver

c. FMO3; liver

d. LPS; kidney

c

Choline, TMA/TMAO lead to what cardiometabolic diseases?

ATHEROSCLEROSIS

thrombosis

SCFAs lead to

blood pressure homeostasis

myocardial repair

True or false: increased TMAO can increase stroke susceptibility

true

The metaorganismal metabolite ________________________________ (PAG) is derived from microbial metabolism of phenylalanine and is involved in the enhancement of platelet thrombotic potential via adrenergic receptors

phenylacetylglutamine

Which of the following are true?

a. the metabolism of phenylalanine produces PAG

b. PAG can decrease risk of heart attack and stroke

c. PAG can increase risk of heart attack and stroke

d. adrenergic receptors increase thrombotic potential

a, c, d

CAD patients had decreased levels of:

a. roseburia

b. faecalibacterium

c. firmicutes

d. shigella

a, b

HTN patients have increased

a. F/B ratio

b. TMAO

c. Ang II

a, b, c

HF patients have increased

a. E. coli

b. S. viridians

c. roseburia

d. Klebsiella pneumonia

e. TMAO

a, b, d, e

Obesity and T2DM patients have increased

a. bacteroides

b. firmicutes

c. tmao

b, c

CKD patients have increased

a. firmicutes

b. bacteroides

c. TMAO

d. urea

e. p-cresol sulfate

a, c, d, e

What are ways to modulate the gut microbiome and prevent cardio-metabolic disorders?

a. prudent dietary patterns

b. physical activity

c. increased choline intake

d. pre/probiotics

e. FMT

f. bariatric surgery

g. high fat diet

a, b, d, e, f

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