This document discusses a study examining the links between intestinal inflammation, sex, and bone health in mice. The study found that male and female mice responded differently to intestinal inflammation caused by the bacteria Helicobacter hepaticus, with males experiencing greater bone loss. The study also found that the probiotic bacterium Lactobacillus reuteri reduced intestinal inflammation and bone loss in male mice, indicating sex determines the intestinal and bone responses to both harmful and beneficial bacteria.
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Sex, guts and healthy bones
1. Sex, guts and healthy bones
Laura McCabe, Ph.D.
Departments of Physiology and Radiology
February 26, 2016
2. Sex, guts and healthy bones
Laura McCabe, Ph.D.
Departments of Physiology and Radiology, MSU
Inflammation
GEORGE
JEN
Intestinal TNF
3. IL-10 -/-
♂ ♀
Adult mice
***
***
0
0.7
1.4
Male
BoneVolume/
BodyMass
Control H. hep Control H. hep
*** **
2-way ANOVA
Gender p ≤ 0.001
H. hep p ≤ 0.001
Gender X H.hep p ≤ 0.001
MALEFEMALEControl H.hep
Femalele
A
**
Control H.hep
FemaleMale
A
B 2-wayANOVA
Gender p≤0.05
H.hep p≤0.001
Sex determines intestinal and bone
responses to “bad” bacteria
H. Hepaticus
Bonedensity
4. BoneDensity
Intestinal Inflammation is Linked to Bone Loss
Colon TNFa levels
r = -0.79
p < 0.0001
0
30
60
0 5 10
Intestinal Pathology
Score
r = -0.76
p = 0.002
0
30
60
0 12 24
5. • In milk, meat, human gut
• Used to treat colic
• Produces anti-microbials
• Anti-inflammatory activity
0
8
16
24
32
MALEBonedensity
*
Control +Lr
*
47%
MALEIntestinal
TNFα/HPRT
0
0.2
0.4
0.6
0.8
1
control lacto
Control +Lr Control ↓E ↓E+Lr
Vertebrae
0
10
20
FEMALE
Bonedensity
Lactobacillus reuteri (LR):
Sex determines intestinal and bone
responses to “good” bacteria
Jejunum
2 million fractures per year due to osteoproosis
Chemical structure of dextran sulfate sodium (DSS), a sulfated polysaccharide, and its biological activities. DSS (1–5% in drinking water or diet) induces colitis in rodents; 30-50KD MW
TNF, IL-17a, ifn-gamma
Mice 14-18 week, 109 cfus
Inhibits gram- bacteria
Humans sometimes need supplementation to maintain high levels in gut
http://www.siliconvalleyfit.com/blog/bid/347252/Can-L-Reuteri-Lower-Your-LDL-Cholesterol
Gram postive
Biogsis owns several strains of this
Lactic acid producing bacteria
Find in food, meat and milk products
L. Reuteri found in human stool in 1960s but also in sheep, chickens, pigs and rodents
Host-Specific strains for each aniaml
Produces reuterin, reutericin 6 and reutericyclin – antimicrobials
Can inhibit gram neg bacteria
Humans don’t always have l reuteri and need supplementation to maintain high levels in gut
Tested in children, healthy adutls and immunosuppressed HIV patients without any adverse effects with 10 to 10 dose units per day.
Found to reudce motor complex and motility
Very potent at reducing gut infections
Very effective against colic – not clear why
Commerical turkeys have increased weight when give LR…However, other studies have revealed it can also help when the growth depression is caused entirely by a lack of dietary protein, and not by contagious disease.[51] This raises the possibility that L. reuteri somehow improves the intestines' ability to absorb and process nutrients.[12]
Low GC content
Journal of Pediatr Gastroenterol Nutr. 2009 Sep;49(3):349-54
Lactobacilli in breast milk and detected in infants
The probiotic that I’ll be focusing on today is…Currently, we have established genetic tools in the lab that will aid in investigating the beneficial functions of L. reuteri. And lastly, there have been demonstrated immunomodulatory activity for this strain.