Module 16- T1D Only Flashcards

1
Q

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

A

21%

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2
Q

Contribution of microbial species to disease

A

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

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3
Q

Kill Beta cells

A

Induced T and B cells

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4
Q

Proof that microbes play role in T1D

A

Provide antibiotics –> No disease

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5
Q

Leaky gut and T1D steps

A

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

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6
Q

BB-DR rats

A

Biobreathing drug resistant predisposed to diabetes but do not get it

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7
Q

BB-DP rats

A

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

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8
Q

Microbes in BB-DP rats

A

Bacteroides - Xanthomonas + Acinetobacter

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9
Q

BB-DR rats

A

Lactobacillus- Clostridium, Flexibacter, Porphyromonas

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10
Q

454-Pyrosequencing

A

Less diverse microbiota in rats over time and less richness

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11
Q

Criteria for selection of microbiota transplant of Lactobacillus

A

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

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12
Q

Onset of T1D

A

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

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13
Q

L. Johnsonii changes in microbiota bacterial counts?

A

No differences

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14
Q

RT-PCR

A

Culture Independent method to see change in microbiota

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15
Q

RT-PCR results

A

More Lactobacillus in healthy and Enterococci in diabetic

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16
Q

Changes in mucosal integrity/architecture

A

Measure villi and necrosis but saw no differences

17
Q

Tight junctions

A

Claudin (and occludin) higher –> Ljo fed

18
Q

L. johnsonii changes

A

Tight junction proteins and cytokines

19
Q

Cytokines changes by L. johnsonii

A

IFNY (and TNFa); lower expression of pro cytokines

20
Q

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

A

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

21
Q

L. Johnsonii modulate IR through

A

TLR7 and TL9; mostly through DNA molecules

22
Q

Mech Ljo use to modulate IR

A

Polarizing-tolerizing mechanism

23
Q

TRL9 induction gives

A

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

24
Q

Phases of T1D testing

A

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

25
Q

Placebo

A

Dried milk

26
Q

Study Design

A

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

27
Q

Ljo led to

A

Significant decrease of symptoms in questionnaire including anxiety and epidermal syndrome

28
Q

Immunotyping of trial

A

Cell types

29
Q

Cell Types that increased upon supplementation

A

Monocytes and NK cells and CD8 cells

30
Q

Cell types that were modified

A

T cell subsets (decreased)

31
Q

CD8 cells…

A

Start to decrease after wash out

32
Q

Th types activation

A

Th1 after 8 weeks and Th17 after 12 weeks

33
Q

In healthy subjects Ljo led to more

A

Circulating IgA

34
Q

Changes in microbiome

A

Larger between each individual than between treatments

35
Q

Risk of Ljo

A

None in healthy

36
Q

Ljo suppresses

A

GI distress syndrome and cephalic syndrome

37
Q

Altered metabolies

A

Tryptophan pathway metabolites after 12 weeks with increasing LAB over time

38
Q

Th subtype mainly increased

A

Th1