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
Grenham et al., MICROBIOTA-GUT-BRAIN AXIS
GUT-BRAIN PATHWAYS Cryan & Dinan, Nature Nurosci Rev
Bailey et al., 999
Antimicrobial treatment induces changes in the gut microbiota and affects behaviour
Microbiota/brain development Borre et al., 4
Antibiotic treatment of mice reduces the density and diversity of intestinal microbial flora Lamouse -Smit et al.,
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
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
S o c ia l In te r a c tio n (s ) 4 6 7 8 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 ) 4 6 7 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
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. 4. 8 7 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 -. -. -.76 ms -. -. ms Key bo ard 8 bsts on 7 7 co py : Channel -. 6. 6. 6 6.7 6.8 6. 9 -..8 Tim e.8.9.9.6.6.6.6.6.6.6.6.64.64.6 seconds 6. 6. untitled Eve nts 4 4 6 6 7 7 8 8 9 9 4 4 s 4 8 6 4 4 6 6 4 7 7 6 8 9 s9 88 DYSB/veh. 8. 6 4 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 8 7. -. -. -. 9 ms -. Keyb oard 8 bs ts on 7 7 co py: 8 Channel 4 8 6 7 8 9 6 6 6 6 64 6 66 67 68 69 7 7 7 7 74 7 s 4 4 7 6 6 4 67 7 8 8 9 8 9 4 s 6 8 4 s Burst Events 6-4 - 4 - D 4 4 6 6 7 7 8 8 9 9 4 DYSB/Prob 4 J -.. -4 EAP slope (mv/ms).. 8 7 9 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 4 6 7 8 9 4 6 7 8 9 4 s 6. 6. 6.4-4 6. 6.6 6. 7 6.8 6.9 6. 6. s 8 7-6 CTL Dysb Keyb oard bs ts Burst on 7 co py: Events Cha nnel 4 4 6 8 6 7 8 9 4 6 8 s 9 4 4 6 6 7 7 8 8 9 9 4 s 8 4
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
Dysbiosis does not affect microglia and glial activation in the PVN, Thalamus and Cortex
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.
All diseases begin in the gut! [Hippocrates, 46-7 BC] Prof. Maione ADHD/ADD ASDs Bipolar disorders Schizophrenia Depression Behaviour: Monica Iannotta Glia morphology: Anna Furiano Electrophysiology: Danilo De Gregorio Psychological support: Livio Luongo and Serena Boccella Usiello lab: brain biomolecular analysis Cuomo lab: gut biomolecular analysis Thank you for the attention