Module 16 Flashcards
1
Q
Congenital Lactose Intolerance
A
Deficiency in b-galactosidase
2
Q
B-galactosidase
A
Digestion of disaccharide lactose
3
Q
Lactose Intolerance Help
A
Intake of fermented dairy instead of milk so LAB produce B-galacotsidase to breakdown lactose in intestine or milk
4
Q
B-galactosidase not function
A
Lactose makes CS of intestine secrete water into intestine and lots of bacterial fermentation –> Production of H, CO2, lactic acid, and acetic acid –> loose stool, bloating, abdominal pain, flatulence
5
Q
Types of Diarrhea Treatments
A
Infantile, Antibiotic-associated, Traveller’s
6
Q
Infantile diarrhea
A
Several viruses and bacteria but mainly rotavirus
7
Q
Leading cause of acute viral gastroenteritis in children
A
Group A Rotavirus (GVA) at about 440,000 deaths/year
8
Q
GVA Mechanism
A
Enhanced permeability of gut epithelial cells to intact proteins and altered handling of antigens in enteric route
9
Q
Steps of RVA
A
Increased permeability of intestinal wall –> More antigens across barrier –> Bigger inflammatory response
10
Q
Why probiotics might help with GVA
A
Enhance mucosal integrity
11
Q
GVA in animal models
A
Rodents and Pigs
12
Q
Bacteria against RVA
A
Lactobacilli casie sp. rhamnosus strain GG and Bifidobacteria bifidum
13
Q
Antibiotic-Associated Diarrhea
A
Otherwise unexplained diarrhea that occurs in association with antibiotics
14
Q
Pseudomembranous colitis
A
C. diff etiological agent
15
Q
Most common cause of antibiotic-associated diarrhea
A
C. diff
16
Q
Antibiotics…
A
Disrupts barrier function of normal microbiota so C. diff can establish itself and produce toxin
17
Q
Antibiotics for C. diff
A
Metronidazole and Vancomycin with recurrence common
18
Q
Probiotics Prevention of C. diff
A
Conflict with B. longum superior to placebo for erythromycin induced diarrhea in 10 healthy and L. GG having lower incidence compared with yogurt placebo
19
Q
Probiotic for C. diff
A
Lactobacillus GG
20
Q
Treatment for C. diff times
A
Ongoing infection or while on antibiotics
21
Q
Psuedomembraneous colitis mechanism
A
Exaggerated response of circulating neutrophils and monocytes due to toxin –> inflamed intestinal tissue and cell death
22
Q
Traveler’s diarrhea
A
Many microbes but most caused by enterotoxigenic E. coli from drinking water in different countries
23
Q
Results of probiotics in TD
A
Conflict depending on strain, vehicle, and dosage (hard to evaluate)
24
Q
Prevalence of H. pylori gastritis
A
50% worldwide
25
Chronic gastritis
H. pylori
26
Increased risk of peptic ulcer disease
H. pylori
27
Increased H. pylori cancers
MALT lymphoma and Gastric Cancer
28
Probiotics for H. pylori
Improve eradication with other anti-therapies and decrease antibiotic related side effects
29
Mechanisms that treat H. pylori
(1) AM substance production
(2) Epithelial cell adhesion and competition
(3) Mucosal barrier stabilization
(4) IR regulation
(5) sIgA secretion
30
AM substance production to treat H. pylori
Bifidobacterium and Enterococcus generate heat stable protein
31
Mucosal barrier stabilization
Tight junction strengthened so pathogen cannot get through
32
Immune response regulation for H. pylori
Probiotics stimulate --> pathogen gets there --> quick IR to clear
33
First line of tolerance
sIgA Secretion
34
For H. pylori treatment
Combo of probiotics more effective in eradication or big proportion elimination
35
Necrotizing Enterocolitis (NEC)
Acute inflammation due to immature intestine that effects 5-10% of low birth rate infants
36
NEC leads to...
High mortality, heavy complication, invalidating sequelae
37
Immaturity of Intestinal barrier
Likely major etiological factors of NEC
38
Probiotics of NEC
Any microbe can invade so any bacteria that can strengthen the intestinal barrier
39
Most probiotic trials on NEC
Focus on impact of intestinal colonization measured by fecal microbiota composition analysis
40
Probiotics for NEC
Variety or mix of strains or synbiotics reduce level of pathogenic bacteria and yeast
41
L. reuteri ATCC 55730
Accelerate GI motility to prevent bacterial overgrowth in NEC
42
B. lactis SNSM I-33446
Faster decrease of intestinal permeability levels in NEC --> preterm barrier function
43
Most trials on NEC focus on
Microbiota to determine if it's the agent of disease
44
IBS
GI disorder characterised by association between recurrent abdominal pain/discomfort and change in stool consistency and frequency
45
IBS categories by symptoms in subgroup
Constipation-predominant, Diarrhea-predominant, Mixed type
46
IBS Cause
Deregulated IR directly related to deterioration of intestinal barrier function
47
Microbiota in IBS
Debate but microbiota likely involved in disease symptoms
48
How microbiota contributes to IBS
(1) Altered fermentation
(2) Harmful modulation of enteric sensorimotor function
(3) Impair intestinal barrier function
(4) Sustained Immune activation without macroscopic signs of inflammation
(5) Harmful modulation of the brain-gut axis
49
IBS symptom score probiotics
Those that increase barrier function
50
IBS has
Lots of scientific debate
51
Chicken or egg approach for
Microbiota causing intestinal barrier disruption in IBS or otehr way
52
Disruption of barrier causes
Inflammation and sustained IR
53
IBS probiotic studies
Mostly in vitro and ex vivo cell culture + animal models such as mice and rats
54
IBS studies work by
Disrupting the intestinal barrier before adding probiotic strain or a mixture
55
Probiotics in IBS can lead to...
Alleviation of symptoms in animals + restoration of barrier function by enhancing tight junction proteins
56
Tight junction proteins
Occludin, E-cadherin, Claudin-1
57
Tight junction proteins produced to help
IBS to enhance barrier function
58
Lost of probiotics and mixtures tested
IBS
59
IBD overall term to describe
CD and UC and Pouchitis
60
Affect any part of bowel but predominately terminal ileum and colon
Chron's Disease
61
Granulomatous, patchy, transmural mononuclear inflammation
CD
62
Only affects the colon
UC
63
Lesions mucosal and continuous
UC
64
UC
Massive neutrophil infiltration, crypt abscesses, loss of goblet cells, epi damage
65
Acute or chronic inflammation of ileal reservoir
Pouchitis
66
Pouchitis
After colectomy and ileal pouch-anal anastomosis following UC
67
Active IBD
Mucosal inflammation + impaired barrier function
68
Remission of CD and UC Requires
Immunosuppressive agents such as corticosteroids, azathioprine, and anti-TNF
69
Probiotics not tested on
Active IBD
70
Probiotics in IBD
Maintaining remission
71
Probiotics for IBD Treated for...
Pouchitis mostly, some UC, unlikely CD
72
Probiotics in constipation
Reduce whole gut transit time and increased stool frequency
73
Probiotic microbes in constipation
Bifidobacterium lactis but not L. casei Shirota
74
Cancer prevention and proboitics
Changes related to tumor induction and promotion
75
Cancer prevention mechanisms
1. Alter intestinal microecology (microbiota effect)
2. Altered intestinal metabolic activity
3. Normalize intestinal permeability
4. Enhanced intestinal immunity
5. Strengthened intestinal barrier mechanisms
76
Altered Microecology (Microbiota effect)
Remove from the microbiome microbes that have ability to turn pro-carcinogens to carcinogens
77
Cancer prevention mostly...
Removal of cancer promoting compounds or inhibition of transformation of non-carcinogens into carcinogens
78
Strengthen intestinal Barrier through
Altering microecology + Altered metabolic activity + normalize intestinal permeability + enhance intestinal immunity
79
Specific Examples of LAB in Cancer prevention
(1) Bind mutagenic amines generated when cooking protein rich food
(2) Degrade nitrosamines
(3) Reduce activity of bacterial B-glucuronidaes, nitroreductases, adn azoreductases
(3) Inhibit quinoline (IQ) induced incidence of colon tumors in rats
(4) Bind aflatoxins (fungal endotoxins that are pro-carcinogens) so they cannot be adsorbed by the intestine
80
2-amino-3-methylimidazol [4,5-f] quinoline (IQ)
Induce intestinal tumors
81
Detrimental to dental health
Sugar fermentation and pH decreases + high buffering capacity of milk products and calcium concentrations that help in protection of dental surfaces
82
Preventative effect of fermented milks and cheeses
Lactobacillus GG colonize oral mucosa and prevent growth of S. sorbinus + S. mutants
83
Nutritional absorption + Specialized barrier function
Intestinal mucosa
84
Front line of intestinal barrier
Single layer of specialized epithelial cells linked together by tight junction proteins (TJ)
85
Factors that support intestinal barrier
Mucins, AM molecules, Immunoglobulins, cytokines
86
Enterocytes
Specialised epithelial cells of the intestine that form single barrier with tight junctions
87
Leaky gut
Barrier factor abnormalities causes intestinal permeability
88
Paneth Cells
Secrete antimicrobial molecules
89
Goblet Cells
Produce mucus
90
Lamina propria
Layer right under epithelial cells that has cells that sense the exterior or secrete IgA with AM activity
91
Leaky gut problems
Microbes or toxins get accross --> exaggerated IR
92
Leaky gut leads to
Autoimmune diseases due to antigens entering the gut lumen --> local and systemic immune responses
93
Diseases arise or exacerbated due to leaky gut
IBD, Celiac disease, Autoimmune hepatitis, T1D, MS, SLE
94
Requirements for gut derived systemic IR
TLR activation + inflammasome stimulation + Dysbiosis + Molecular mimicry + Breech of barrier
95
Inflammasome
Protein complexes in different cells that induce secretion of IL1B and IL-18
96
Molecular mimicry
Antigens similar to our own is original target for the IR so antibodies get directed against our own cells
97
Chronic immune-mediated inflammatory liver disease with uncertain cause
Autoimmune Hepatitis
98
Susceptibility factor of autoimmune hepatitis
MHC
99
Key antigen targets for autoimmune hepatitis
Cytochrome P450 2D6 (CYP2D6) + formiminotransferase cylcodeaminase
100
Molecular mimicry example
CYP2D6 and HCV, HSV, CMV --> autoimmune hepatitis
101
Steps to AI Hepatitis
Dysbiosis of intestine --> bacterial ligands and toxins get into bloods stream --> to liver through portal veins --> activate T-cells --> exacerbate responses or activation of inflammasome --> Inflammation, liver damage, hepatic fibrosis
102
AI associated with...
Dysbiosis evidenced by proteins binding intestinal epithelial cells being reduced in patients with A disease + LPS increased + decreased intestinal anaerobes (Bifidobacterium and Lactobacillus)
103
Structural proteins reduced in AI hepatits
Zona occludens 1 and occludin
104
AI and probiotics
Not addressed yet due to no animal model
105
Severe persistent inflammation that leads to tissue damage of multiple organs
Systemic Lupus Erythematosus
106
Women are ... more likely to get SLE
9x
107
SLE characterised by
Autoantibodies, auto reactive T-cells, Abnormal generation of proinflammatory cytokines
108
Therapeutic for SLE include
Restoring imbalanced cytokines and deficient immune cells
109
Triggers of SLE
Genetics, environment, unknown --> activation of IR against self Ag --> auto reactive B cells, pro cytokines, and inflammatory T cells
110
Inducers of SLE
LPS penetrated intestinal epithelium and translocating to tissues
111
Spontaneous development of lupus in mice
TLR4 increased induced by LPS
112
Treatment of SLE
Antibiotics to rid of commensal gut flora + Immunoregulatory probiotics
113
Immunoregulatory probioitcs
Enhance Treg cells and control inflammatory response --> induce tolerance
114
Before T1D disease onset
Impaired intestinal barrier functions (microbiome trigger)
115
Pancreatic B cells
Destroyed by autoimmunity in T1D
116
Zonulin
Pathogenic role of intestinal permeability in T1D depended on it; relies on bacterial colonization
117
Bacteria to T1D
Bacterial colonization --> Zonulin colonization --> increased intestinal permeability --> pathogenesis
118
Zonulin inhibitor in rats
Reversion of intestinal barrier dysbiosis relives symptoms of T1D
119
T1D faucets
Altered microbiota + leaky gut + altered mucosal immunity
120
T1D perfect storm
Altered microbiota —> exacerbated IR because increased presentation of antigen to APCs that get through the leaky gut —> T-cells activation —> cytokine relasesa nd secretion of autoantiboides in pancreas —> perfect storm because everything must act together for autoimmune reaction
121
Contributes to T1D development
Microbial Translocation
122
Streptozotocin-induced T1D
Gut bacteria able to translocate into PLNs and contribute to T1D + had a distinct microbiota
123
PLNs translocation proof
Treat streptozotocin mice with antibiotics --> PLNs sterile and disease attenuated
