Sex, guts and healthy bones

Laura McCabe, Ph.D.Departments of Physiology and Radiology

February 26, 2016

Sex, guts and healthy bones

Laura McCabe, Ph.D.Departments of Physiology and Radiology, MSU

Inflammation

GEORGE

JEN

Intestinal TNF

IL-10 -/-

♂ ♀

Adult mice

MALE FEMALE

Sex determines intestinal and bone responses to “bad” bacteria

H. Hepaticus

Bone

den

sity

Bon

e D

ensi

ty

Intestinal Inflammation is Linked to Bone Loss

Colon TNFa levels

r = -0.79p < 0.0001

0 1 2 3 4 5 6 7 8 9 100

30

60

Intestinal Pathology Score

r = -0.76p = 0.002

0 12 240

30

60

• In milk, meat, human gut• Used to treat colic• Produces anti-microbials• Anti-inflammatory activity

0

8

16

24

32

MA

LE B

one

dens

ity

*

Control +Lr

*47%

MAL

E In

testi

nal

TNFα

/HPR

T

co n tro l lacto

0

0.2

0.4

0.6

0.8

1

Control +Lr Control ↓E ↓E+Lr

Verte

brae

0

10

20

FE

MAL

EBo

ne d

ensit

y

Lactobacillus reuteri (LR):

Sex determines intestinal and bone responses to “good” bacteria

Inflammation

Immune cells

Bacteria + products

Blood

Inte

stin

alEp

ithel

ial B

arrie

r

Tightjunctions

Gut environment modulators:

Probiotics, Prebiotics, Antibiotics, New Compounds

Other signals:Incretins, Serotonin,

Neural,Distal Inflammation

Working Model

Bone marrow