final exam Flashcards
1
Q
penicillin mechanism of action
A
binds PBP –> inhibit –> disrupts cross-linking rxns and disrupts PGN synthesis
2
Q
what forms carbohydrate backbone of PGN
A
NAG and NAM
3
Q
What binds to NOD1 receptors
A
Tri-DAP
Tetra-DAP
iE-DAP
(gram negative)
4
Q
what is M-tetra-DAP formed from
A
L-alanine
D-glutamine
meso-DAP
D-alanine
5
Q
what binds to NOD2 receptors
A
MDP
(gram positive)
6
Q
what is iE-DAP formed from
A
D-glutamine
meso-DAP
7
Q
what is M-tri-DAP formed from
A
L-alaine
D-glutamine
meso-DAP
8
Q
what is MDP formed from
A
L-alanine
D-iso glutamine
9
Q
what enzyme breaks out NAM
A
lytic transglycosylase
10
Q
what enzyme cut fragements of polypeptides (except for one connected to NAM)
A
endopeptidase
11
Q
NOD1 signal path
A
NOD1 –> RIP2 –> (p65,p50,IkB) –> NFkB –> cytokines (inflam response)
12
Q
NOD2 signal path
A
NOD2 –> RIP2 (NOD1 path) –> CARD9 –> MKKs –> AP1 –
13
Q
teichoic acid regulates movement of
A
cations
14
Q
3 main parts of LPS
A
Lipid A, core polysaccharide and O polysaccharide
15
Q
how is gram - different form gram +
A
outer membrane, THIN PGN layer, LPS, NO teichoic acid
16
Q
endotoxemia
A
high level of LPS
17
Q
end result of TLR2 and TLR4 signalling
A
activate NFkB - increases inflammatory cytokine production
18
Q
ratio of bacteria cells to human cells in body
A
10:1
19
Q
In general, how do disease states affect gut microbiota
A
decreases microbial abundance and diversity
20
Q
Two major phyla in gut microbiota
A
Firmicutes and bacteroidetes
21
Q
What are some factors that affect that affect colonization of gut microbiota
A
-c-section
-formula feeding
-maternal antibiotics
-indoor living
-excess sanitization
22
Q
what are symbionts
A
bacteria with health-promoting functions
23
Q
what are commensals
A
permanent residents of the microbiota (no benefit or detriment to our knowledge)
24
Q
What are pathobionts?
A
permanent residents of the microbiota that have the potential to induce pathologies
25
what are probiotics
live microbes that are ingested into the body and intended to exert a beneficial effect
26
What does C. difficile infection do to the gut after 30 hours of exposure?
damages epithelial cells, triggering inflammation
27
What does C. difficile infection do to the gut after 36 hours of exposure?
inflamed epithelial cells burst and die; spores leave colon via diarrhea
28
What is the standard of care for patients with 3 recurrent C. difficile infections?
patients get a fecal microbiota transplant from a healthy donor
28
How does the mucus barrier differ in germ-free mice?
mucus barrier is much thinner
28
How does the gut microbiota have health benefits?
supplies essential nutrients, metabolizes non-digestible components, defends against pathogens, and contributes to structure of epithelial barrier
28
How do Bifidobacterium spp. play a role in obesity?
anti-obesity effects in microbiota
28
What are the main bacterial phylums present in the gut microbiota?
High abundance: Bacteroidetes, Firmicutes,
Low abundance: Actinobacteria, Proteobacteria, and Verrucomicrbia
29
How does Akkermansia muciniphila play a role in obesity?
anti-obesity effects in microbiota
30
How does Parabacteroides distasonis play a role in obesity?
increased in obesity; increases NFkB expression
31
How do citrobacter sp. plau a role in IBD
increases H2S production, increases inflammation, cause epi cell death
32
mucin in inner layer
muc1 and muc2
32
mucin in outer layer
muc2
32
apoptotic cells are found where
top of epi barrier
32
goblet cells function
secrete mucins
32
stem cells found where
base of crypt
33
Fcgbp function
cross-link mucins (outer layer)
34
what mucins are O and N glycosylated
muc 1 and muc 2
34
mucin only O-glycosylated
muc 2
35
what happens when bacteria gets through mucus layer
mucus and antimicrobial proteins are secreted, inflammation is stimulated OR epi cells die, and extracellular domains of mucins are released which coat & kill the bacteria
36
What are the effects of pathogenic bacteria secreting toxins in the mucus layer?
toxins disrupt tight junctions, induce epithelial cell apoptosis, and disrupt mucus production
37
What is the primary mucin produced in the stomach?
muc5AC
37
What is the primary mucin produced in the small and large intestines?
muc2
37
How does the size of the mucus layer differ through the GI tract?
mucus layer is thicker in colon than stomach and SI
38
What are anti-microbial proteins produced by?
primarily by paneth cells and epi cells, also by immune cells
39
What are some types of anti-microbial proteins/peptides?
defensins, REGs, cathelicidins, lysozymes, and IgA
40
How do cathelicidins have anti-microbial effects?
LL37 promotes wound healing and modulates the adaptive immune response
41
What gene encodes the peptide LL-37?
CAMP gene
42
How are defensins activated?
pro-defensins are proteolytically cleaved by trypsins and peptidases
43
What enzyme inhibitors prevent activation of defensins?
α1-protease inhibitor and α1-anti-trypsin
44
What is REG3y?
anti-microbial protein secreted by intestinal epithelial cells that have bactericidal properties against gram + bacteria
45
How does bean supplementation affect mucosal barrier defense?
increases expression of IgA, REG3y, mucins (muc2), and tight junction proteins (occludins & JAM-A); increases microbiota activity
46
What are some characteristics of obese adipose tissue?
adipocyte hypertrophy, insufficient angiogenesis, immune cell infiltration, low-grade inflammation, and insulin resistance
47
What adipokines are increased in obese adipose tissue?
TNFα, IL-6, MCP-1, and leptin
48
How does the number and function of Tregs change in obesity?
decreased; function is suppressed by leptin
49
How does the production and secretion of adiponectin change in obesity?
decreased; insulin-sensitizing and anti-inflammatory effects are lost
50
How does the production and secretion of IL-10 change in obesity?
decreased; anti-inflammatory effects are lost
51
How does the number of M1 and M2 macrophages change in obesity?
increased M1 macrophages, decreased M2 macrophages
52
How does DHA supplementation in obese patients affect macrophage polarization?
DHA increases M2 macrophages and decreased M1 macrophages
53
How do M1 macrophages stimulate inflammation in obesity?
produces inflammatory cytokines (MCP-1, TNFα, IL-6) and expresses iNOS which produces nitric oxide
54
What binds to the surface receptor GPR120?
n-3 PUFAs
55
What is the end result of n-3 PUFA GPR120 signalling in M1 macrophages?
NFkB activation is suppressed, reducing inflammatory cytokine production (which normally suppress insulin signalling)
56
What is the end result of n-3 PUFA GPR120 signalling in adipocytes?
GLUT4 translocation is stimulated, restoring impairments in glucose uptake
57
What happens when TNFa and IL-6 inhibit IRS-1?
no glucose translocation and uptake occurs, making this cell insulin-resistant
58
How does GLP-1 improve glucose homeostasis?
controls appetite, stimulates insulin production, promotes beta cell growth, and reduces insulin resistance
59
What are some of the beneficial effects of resveratrol supplementation?
limits HFD-induced weight gain, increased enterocyte expression of GLP-1, improves glucose homeostasis, increases adiponectin, decreases liver lipid accumulation
60
What are some of the beneficial effects of turmeric?
reduces STAT3 activation, reduces NFkB activation, upregulates PPARy activation, reduces FFA release, and improves insulin sensitivity
61
What are some of the beneficial effects of quercitin in obesity?
reduces M1 macrophages, reduces inflammatory mediator production, reduces TLR4 expression, reduces NFkB activations, increases skeletal muscle glucose uptake
62
What are some of the beneficial effects of cocoa in obesity?
reduces NFkB activation, TNFα, IL-6, plasma LPS; increases GLP-2
63
What are three families of medicinal plants that reduce the incidence of obesity and type 2 diabetes?
Rubiaceae, Spindaceae, and Rhamnaceae families
64
If a germ-free mouse is given the microbiota of an obese mouse, what happens?
mouse adopts donor phenotype and becomes obese
65
If the microbiota of a lean donor is given to an obese recipient, what happens?
insulin sensitivity is restored in obese recipient
66
How does the microbiota composition change in response to HFD?
↑ Firmicutes, ↓ Bacteroidetes, ↓ Akkermansia muciniphilia, ↓ Bifidobacterium, ↓ Faecalibacterium prausnitzii
67
Why is a low gene count an indicator of obesity?
LGC individuals exhibit more adiposity, insulin resistance, dyslipidemia, and more inflammatory mediator production
68
Why can artificial sweeteners be damaging?
they drive the development of glucose intolerance through alterations to the microbiota
69
What are types of insoluble fibre?
cellulose and lignan
70
What are some types of soluble fibre?
xylans, oligosaccharides, fructans, chitins, beta-glucans, inulin, and pectins
71
How does SCFA concentration change throughout the colon?
decreases
72
What are 2, 3, and 4-carbon SCFAs called?
acetate (2C), propionate (3C), butyrate (4C)
73
How does pH change throughout the colon?
increases
74
What SCFA transporters are found in the apical border?
MCT1 and SMCT1
75
What SCFA transporters are found in the basolateral membrane?
MCT4 and MCT5
76
What binds to the G-coupled protein receptors GPR41, GPR43, and GPR109a?
SCFAs
77
What beneficial effects does SCFA signalling have in host tissues?
increases FFA oxidation in liver & skeletal muscle, decreases NFkB activation, increases IL-10 production, stimulates FOX3 expression & Treg activation
78
What are some major butyrate-producing bacteria?
Prevotella species and Roseburia species
79
How does butyrate improve gut barrier function?
decreases colonic pH (↓ growth of pathogenic bacteria), inhibits NFkB, increases tight junction assembly, and stimulates production of muc2, IgA, & Tre-foil factor 3
80
What enzymes digest pectin?
lyase, alpha-glucosidase, polygalactouronase
81
What enzymes digest starch?
type-1 pullulanase
82
What enzymes digest inulin?
inulinase, inulin lyase, beta-fructofuranosidase
83
What enzymes digest cellulose?
endoglucanase, beta-glucosidase
84
Which bacteria have a preference for resistant starch?
Bacteroides thetaiotaomicron, Bifidobacterium spp., Ruminococcus bromii, Roseburia spp.
85
Which bacteria have a preference for pectins?
Bacteroides spp. and Lachnospira pectinoschiza
86
Which bacteria have preference for inulin and oligosaccharides?
Bifidobacterium spp., Collinsella aerofaceins, Eubacterium rectale, Raecalibacterium praunitzii, Roseburia spp.
87
Which bacteria have a preference for cellulose?
Ruminococcus spp., Fibrobacter spp., Clostridium spp.
88
Which bacteria have a preference for host glycoproteins?
Akkermansia muciniphila
89
What happens with prebiotic fibre supplementation for obese people?
↓ plasma LPS, ↑ L cells, ↑ plasma GLP-1, ↓ plasma TG, ↓ muscle lipid content (improved gut barrier integrity & metabolic outcomes)
90
How does the abundance of Akkermansia muciniphila change with obesity and T2 diabetes?
decreases abundance
91
How does the abundance of REG3y change with obesity?
decreases abundance
92
How can prebiotic supplementation of oligofructose to HFD affect Akkermansia mucinophila?
HFD/obesity-associated loss of A. mucinophila is reversed
93
How can prebiotic supplementation of oligofructose to HFD affect macrophage infiltration?
reduces M1 macrophage infiltration into adipose tissue
94
How do Lactobacillus spp. improve the obese phenotype?
reduces body weight gain, reduces visceral adipose tissue, improves fasting blood glucose, etc.
95
How do Bifidobacterium longum and Bifidobacterium pseudocatenalatum improve the obese phenotype?
reduces body weight gain and visceral adipose tissue
96
How does Propionibacterium freudenreichi improve the obese phenotype?
reduces appetite by producing propionate
97
How can probiotic supplementation of Akkermansia muciniphilia to HFD improve the obese phenotype?
↓ M1 macrophages, ↓ fasting blood glucose, ↓ insulin resistance, ↓ fat mass, and improves barrier integrity by ↑ mucus production & ↑ Reg3y expression
98
Why is DHA incompatible with cholesterol in lipid rafts?
DHA has a high degree of unsaturation
99
How does cancer rely on lipid rafts?
pathways involved in cell proliferation, metastasis, and tumour promotion rely on lipid rafts
99
What happens when DHA is added to lipid rafts?
size of lipid raft increases, causing less efficient protein-protein interactions within signalling cascades
100
How does IBD rely on lipid rafts?
IL-6R localizes to lipid rafts, which is required for Th17 cell activation
101
How does obesity rely on lipid rafts?
TLR2, TLR4, α5β1 integrin, leptin receptor, TNFα receptor, and IL-6R localize to lipid rafts
102
What are the two clinical conditions of IBD?
ulcerative colitis and Crohn's disease
103
How does the appearance of the colon change in IBD?
in UC, ulcers are found within the mucosa; in CD, there is muscle hypertrophy and a cobblestone appearance (also some ulcers)
103
What are the symptoms of IBD?
abdominal pain, diarrhea, nausea, diminished appetite, weight loss, fever, anemia, and fatigue
104
What are some complications of IBD?
resistance to drug therapy, perforation of bowel wall, and increased colorectal cancer risk
105
How does the abundance of Firmicutes change in IBD?
decreases abundance
106
How does the abundance of Bacteroidetes change in IBD?
decreases abundance
107
Which bacteria have an increased abundance in IBD?
Helicobacter spp. and Enterococcus faecalis
108
Which bacteria have a decreased abundance in IBD?
Prevotella spp., Roseburia spp., and Faecalibacterium prausnitzii
109
How does the abundance of Helicobacter spp. change in IBD?
increases abundance
110
How does the abundance of Prevotella spp. change in IBD?
decreases abundance
111
How does hydrogen sulfide (H2S) impact host function?
decreases ATP production (by inhibiting cytochrome-C oxidase activity), induces TNFα production, functions as a ROS, and kills off core microbes
112
What are some typical H2S producers?
Proteobacteria, Citrobacter, Pseudomonas, Salmonella, and E. Coli
113
How does the production of butyrate change in IBD?
decreases
114
What is creeping fat?
hypertrophic mesenteric fat that wraps around the inflammed colon (>50% colon coverage) in IBD
115
What are the phenotypic features of creeping fat?
fibrosis, secretion of inflammatory mediators, macrophage infiltration, increased ROS production
116
How does the abundance of Tregs change in IBD patients?
decreases
117
How does the abundance of Th17 cells change in IBD patients?
increases (which drives chronic inflammation)
118
foods to avoid w IBS
FODMP
fermentable, oligosaccharide, disaccharide, monosaccharide
polyphenol
119
How can rutin (found in asparagus) benefit IBD patients?
improves wound healing/epithelial barrier restoration and reduces MMP activation
120
How can green tea polyphenols benefit IBD patients?
decreases NFkB activation, colonic tissue damage, and ROS production
121
How can n-3 PUFAs benefit IBD patients?
reduces inflammatory mediator production, Th17 activation, and colonic tissue damage
122
How can curcumin benefit IBD patients?
decreases STAT3 & NFkB activation (alone), and causes remission in UC patients (with drug treatment)
123
aim of dietary interventions in IBD
delay disease relapse or extend period of time in remission (more time to rebuild colon)
124
fecal calprotectin
correlate w inflammation in colon
125
fecal immunochemical test (FIT)
biomarker of mucosal healing
126
fecal lactoferrin
released from neutrophils and epi cells during an active inflam response in iBD
127
fecal metalloproteinases (MMPs)
released by neutrophils and cell types
-not as effective in patients w crohns disease
128
fecal myelpreoxidase (MPO)
released from neutrophils and monocytes to kill microorganisms
-high MPO levels refelct active IBD and tissue damage
129
what does protein fermentation produce
ammonia
p-cresol and phenol
indole and skatole
130
ammonia
-lower butyrate transporter expression by epi cells
-lower epi barrie integrity and function
131
p-cresol and phenol
tyrosine metabolites
-DNA damage, alter cell cycle
-transformed epi cell proliferation
-low epi-cell proliferation
(carb ferm inhibits production of p-cresol)
132
indole and skatole
trptophan metabolites
-alters nervous system function
-enhance neurodevelopmental or psychiatric diseases
-higher production of indole in rates = anxiety-like behaviour
*INDOLE-lower epi inflammtion and improve barrier function (has SOME good properties)
133
higher fiber intake and protein ferm
alters ability of protein fem products to interact w mucosa and cause bad effects
134
bacteroids fragilis
increase in IBD, increase host inflam and IBD relapse
