Francesca Guida. Seconda Università di Napoli
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1 Lactobacillus casei DG restores dysbiosis-induced gut inflammation, depressive behaviour and recognition memory deficit associated with physiological alterations in the hippocampus Francesca Guida Seconda Università di Napoli
2 Grenham et al., MICROBIOTA-GUT-BRAIN AXIS
3 GUT-BRAIN PATHWAYS Cryan & Dinan, Nature Nurosci Rev
4 Bailey et al., 999
5 Antimicrobial treatment induces changes in the gut microbiota and affects behaviour
6 Microbiota/brain development Borre et al., 4
7
8 Antibiotic treatment of mice reduces the density and diversity of intestinal microbial flora Lamouse -Smit et al.,
9 Lactobacillus casei reduces gut inflammation in dysbiotic mice Jejuneum Duodenum Ileum Colon Fold Increase relative to CTL (a. u.) Fold Increase relative to CTL (a. u.) A B 4 TNF C 4 IL D Fold Increase relative to CTL (a. u.) CTL Dysb Dysb/Veh Dysb/Prob 4 GFAP CTL Dysb Dysb/Veh Dysb/Prob * Fold Increase relative to CTL (a. u.) Fold Increase relative to CTL (a. u.) 4 CTL Dysb Dysb/Veh Dysb/Prob 4 SB CTL Dysb Dysb/Veh Dysb/Prob E CTL Dysb Dysb/Veh Dysb/Prob * * * * Fold Increase relative to CTL (a. u.) IL β TNFα inos GFAP SB F α Actin 4 inos * * * CTL Dysb Dysb/Veh Dysb/Prob Duodenum Jejuneum Ileum Colon ZO- Cx-4 4 C t C t
10 Lactobacillus casei DG reduces depressive-like behaviour in dysbiotic mice Forced swimming test Immobility time (sec) 9 6 * Tail suspension CTL Dysb Dysb/veh Dysb/Prob Immobility time (sec) 9 6 * Probiotic restores BDNF levels in dysbiotic mice CTL Dysb Dysb/veh Dysb/Prob
11 S o c ia l In te r a c tio n (s ) Lactobacillus DG normalizes the altered social recognition memory in dysbiotic mice N e w S o c ia l In te ra c tio n (s ) Three chamber social interaction G O b je c t M o u s e I M o u s e II M o u s e I ## ## C T L D y sb D y s b /v e h D y s b /P ro b C T L D y sb D y s b /v e h D y s b /P ro b S e s s io n I S e s s io n II
12 9 Dysbiosis induces changes on firing activity of CA pyramidal neurons in dorsal hippocampus 8 7 A 6 unti tl ed Eve nts B. mm. CTL.. dhip(ca) AP:-.4 mm L:.- mm V:.- mm Spikes/s 8 7 Dysb Dysb/veh Dysb/Prob EAP amplitude (mv) H.. CTL.. amplitude. 6 mv.. untitled volt. untitle d volt amplitude.. Dysb. slope -. 6 mv slope ms ms Key bo ard 8 bsts on 7 7 co py : Channel Tim e seconds untitled Eve nts s s9 88 DYSB/veh Dysb CTL. Dysb/veh Dysb/Prob Keyb oard bs ts on 7 co py: 8 Cha nnel 6 mv unti tl e d vol t 8 Keyb oard bs ts on 7 7 co py: Cha nnel 6 untitled Eve nts ms -. Keyb oard 8 bs ts on 7 7 co py: 8 Channel s s s Burst Events D DYSB/Prob 4 J EAP slope (mv/ms) C I -. CTL Dysb - 6 mv untitled volt CTL ms ms -. Spikes/s Dysb/veh Dysb/Prob -. Burst Events untitled Eve nts Dysb 4 unti tl ed Events CTL 6 -. Keyboard 8 bsts on 7 7 co py: Channel Keyb oard bs ts on 7 co py: Cha nnel Spikes/s 8 percentage of spikes per burst (%) * 6 number of burst in s(#) firing rate (spikes/s) G -. 4 F Keyb oard bs ts on 7 co py: 8 Cha nnel. untitled mv mv 66mV 4 E. - - ms - -4 Key b oard 8 bs ts on 7 7 co p y: Cha nnel s s CTL Dysb Keyb oard bs ts Burst on 7 co py: Events Cha nnel s s 8 4
13 Dysbiosis and probiotic effects on hippocampal microglia and glial activation Ctl Dys Ctl Dys Dys/Veh Dys/Prob Dys/Veh Dys/Prob 8 TOTAL IBA+ ACTIVATED IBA+ 8 TOTAL GFAP ACTIVATED GFAP Cells number/ µm 6 4 ** ** o Cells number/ µm 6 4 ** ** o CTL DYS DYS/VEH DYS/PROB CTL DYS DYS/VEH DYS/PROB
14 Dysbiosis does not affect microglia and glial activation in the PVN, Thalamus and Cortex
15 Summary Antibiotics-induced dysbiosis causes gut inflammation and sickness behaviour Dysbiosis causes BDNF signalling modulation in the hippocampus Dysbiosis induces microglia/astrocytes phenotypic changes in the brain Dysbiosis induces electrophysiological changes in hippocampal pyramidal neurons Probiotic daily treatment reduces sickness behaviour and brain biochemical/functional changes Restoring the balance of the microbiota gut brain axis offers promising beneficial therapeutic effects in neurodevelopmental disorders associated with gastrointestinal pathologies.
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Supplementation of piglet feeds with hydrolyzed brewery yeast (Progut ) has given valuable benefits in piglet production At weaning, piglets have to adapt rapidly to major changes in their nutrition and
TITLE: Altered Astrocyte-Neuron Interactions and Epileptogenesis in Tuberous Sclerosis Complex Disorder
AWARD NUMBER: W81XWH-12-1-0196 TITLE: Altered Astrocyte-Neuron Interactions and Epileptogenesis in Tuberous Sclerosis Complex Disorder PRINCIPAL INVESTIGATOR: Dr. David Sulzer, Ph.D. CONTRACTING ORGANIZATION:
Gut-Brain Axis and Behavior
Evolution of Human Microbiota Isolauri E, Sherman PM, Walker WA (eds): Intestinal Microbiome: Functional Aspects in Health and Disease. Nestlé Nutr Inst Workshop Ser, vol 88, pp 45 53, ( DOI: 10.1159/000461732
Supplementary Table 1 Gene clone ID for ShRNA-mediated gene silencing TNFα downstream signals in in vitro Symbol Gene ID RefSeqID Clone ID
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 Supplementary Table 1 Gene clone ID for ShRNA-mediated gene silencing TNFα downstream
CHARACTERISTICS. Recovery rate. Spore of Bacillus licheniformis
Targeted protection B-Act is a probiotic feed additive consisting of viable spores of a unique Bacillus licheniformis strain (Strain Identification Number DSM 2871). CHARACTERISTICS Bacillus licheniformis