Module 16- T1D Only

Question 1

Between 2001 and 2009 there was a … increase in T1D for people under 20

Answer 1

21%

Question 2

Contribution of microbial species to disease

Answer 2

Metabolic network + Dynamic equilibrium with themselves and our cells + Innate and acquired defensive systems imbalanced

Question 3

Kill Beta cells

Answer 3

Induced T and B cells

Question 4

Proof that microbes play role in T1D

Answer 4

Provide antibiotics –> No disease

Question 5

Leaky gut and T1D steps

Answer 5

Antigen gets through leaky gut –> activate APC in lamina propria –> cytokine release –> T and B cell activation –> kill beta cells

Question 6

BB-DR rats

Answer 6

Biobreathing drug resistant predisposed to diabetes but do not get it

Question 7

BB-DP rats

Answer 7

Biobreathing diabetes prone rats that get diabetes between day 17 and 110

Question 8

Microbes in BB-DP rats

Answer 8

Bacteroides - Xanthomonas + Acinetobacter

Question 9

BB-DR rats

Answer 9

Lactobacillus- Clostridium, Flexibacter, Porphyromonas

Question 10

454-Pyrosequencing

Answer 10

Less diverse microbiota in rats over time and less richness

Question 11

Criteria for selection of microbiota transplant of Lactobacillus

Answer 11

From 500 colonies –> Found in humans, probiotic properties reported (tolerance to bile and acid), no antagonistic effect to other Lactobacillus species

Question 12

Onset of T1D

Answer 12

Days 69-110 –> gibe bacteria orally pre-weaning or post-weaing (immediate or after start of solid food) –> only difference in post weaning

Question 13

L. Johnsonii changes in microbiota bacterial counts?

Answer 13

No differences

Question 14

RT-PCR

Answer 14

Culture Independent method to see change in microbiota

Question 15

RT-PCR results

Answer 15

More Lactobacillus in healthy and Enterococci in diabetic

Question 16

Changes in mucosal integrity/architecture

Answer 16

Measure villi and necrosis but saw no differences

Question 17

Tight junctions

Answer 17

Claudin (and occludin) higher –> Ljo fed

Question 18

L. johnsonii changes

Answer 18

Tight junction proteins and cytokines

Question 19

Cytokines changes by L. johnsonii

Answer 19

IFNY (and TNFa); lower expression of pro cytokines

Question 20

Addition of TNF-a to epi cells and look at cytokine production

Answer 20

No effect at higher concentrations but does induce immune system by chemokine that prevent later IR

Question 21

L. Johnsonii modulate IR through

Answer 21

TLR7 and TL9; mostly through DNA molecules

Question 22

Mech Ljo use to modulate IR

Answer 22

Polarizing-tolerizing mechanism

Question 23

TRL9 induction gives

Answer 23

Increased paneth cells that secrete AM molecules found at the bottom of crypts –> more secretion of AM molecules

Question 24

Phases of T1D testing

Answer 24

Proof of concept –> Phase one on healthy –> Phase two on disease –> phase 3 on kids to prevent onset

Question 25

Placebo

Answer 25

Dried milk

Question 26

Study Design

Answer 26

Baseline –> Ljo N6.2 or placebo –> wash out –> look at blood and stool samples

Question 27

Ljo led to

Answer 27

Significant decrease of symptoms in questionnaire including anxiety and epidermal syndrome

Question 28

Immunotyping of trial

Answer 28

Cell types

Question 29

Cell Types that increased upon supplementation

Answer 29

Monocytes and NK cells and CD8 cells

Question 30

Cell types that were modified

Answer 30

T cell subsets (decreased)

Question 31

CD8 cells…

Answer 31

Start to decrease after wash out

Question 32

Th types activation

Answer 32

Th1 after 8 weeks and Th17 after 12 weeks

Question 33

In healthy subjects Ljo led to more

Answer 33

Circulating IgA

Question 34

Changes in microbiome

Answer 34

Larger between each individual than between treatments

Question 35

Risk of Ljo

Answer 35

None in healthy

Question 36

Ljo suppresses

Answer 36

GI distress syndrome and cephalic syndrome

Question 37

Altered metabolies

Answer 37

Tryptophan pathway metabolites after 12 weeks with increasing LAB over time

Question 38

Th subtype mainly increased

Answer 38

Th1