Extracellular Vesicles Derived from Lactobacillus plantarum Increase BDNF Expression in Cultured Hippocampal Neurons and Produce Antidepressant-like Effects in Mice

Abstract

Gut microbiota play a role in regulating mental disorders, but the mechanism by which gut microbiota regulate brain function remains unclear. Gram negative and positive gut bacteria release membrane-derived extracellular vesicles (EVs), which function in microbiota-host intercellular communication. In the present study, we investigated whether Lactobacillus plantarum derived EVs ( L -EVs) could have a role in regulating neuronal function and stress-induced depressive-like behaviors. HT22 cells treated with the stress hormone glucocorticoid (GC; corticosterone) had reduced expression of Bdnf and Sirt1 , whereas L -EV treatment reversed GC-induced decreased expression of Bdnf and Sirt1 . The siRNA-mediated knockdown of Sirt1 in HT22 cells decreased Bdnf4 , a splicing variant of Bdnf , and Creb expression, suggesting that Sirt1 plays a role in L -EV-induced increase of BDNF and CREB expression. Mice exposed to restraint for 2-h daily for 14 days (CRST) exhibited depressive-like behaviors, and these CRST-treated mice had reduced expression of Bdnf and Nt4/5 in the hippocampus. In contrast, L -EV injection prior to each restraint treatment blocked the reduced expression of Bdnf and Nt4/5 , and stress-induced depressive-like behaviors. Furthermore, L -EV treatment in CRST-treated mice also rescued the reduced expression of Bdnf , and blocked stress-induced depressive-like behaviors. These results suggest that Lactobacillus derived EVs can change the expression of neurotropic factors in the hippocampus and afford antidepressant-like effects in mice with stress-induced depression.

Proteomic profile of extracellular vesicles released by Lactiplantibacillus plantarum BGAN8 and their internalization by non-polarized HT29 cell line

“…2 B) showed the highest abundance (43.8%) in the range between 41 and 60 nm, followed by 20–40 nm (about 20%), and the remaining (about 36%) with a bigger size (between 61 and 140 nm). In spite of the scarce available data, we consider that this size distribution is similar to that reported in literature for bacterial EVs of lactobacilli strains 25 – 28 , specifically for L. plantarum 19 , 29 , whereas the reported range of EVs from pathogenic Gram-positive bacteria seems to be slightly higher, between 10 and 400 nm 6 .

Figure 2 Extracellular vesicles purified from L. plantarum BGAN8 cell-free supernatants.

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“…Just to summarize some of the most recent studies, it has been showed that EVs released by probiotics are able to interact with pattern recognition receptors (PRR) of host cells initiating the downstream immune response modulation which, contrary to that induced by pathogens (pro-inflammatory) is more tolerogenic 15 – 18 . Additionally, EVs released by L. plantarum were able to in vivo regulate the brain function being able to reduce the stress-induced depression in mice 19 . Therefore, the EVs released by probiotics, or by the intestinal microbiota, could have multiple applications on human health 6 , 20 , 21 .…”

Lactobacillus Rhamnosus GG Affects the BDNF System in Brain Samples of Wistar Rats with Pepsin-Trypsin-Digested Gliadin (PTG)-Induced Enteropathy

“…The effectiveness of probiotic supplementation in the reduction of psychological symptoms [42,43] and as an alternative treatment for CD [25] are nowadays the objects of investigation. Indeed, recent results from clinical trials [44], animal models [45], and in vitro studies [46] indicate that the Lactobacillus administration up-regulates BDNF expression.…”

Fitness of Outer Membrane Vesicles From Komagataeibacter intermedius Is Altered Under the Impact of Simulated Mars-like Stressors Outside the International Space Station

“…In spite of significant shifts, occurring in immune function pathways under spaceflight, vaccination is quite possible and T-cell response is expected to be adequate (Iosim et al, 2019). OMVs could also be potentially employed for treating stress-induced depression of crew members during spaceflight (Choi et al, 2019) or amelioration of metabolic dysfunctions (Ashrafian et al, 2019).…”

“…A growing body of preclinical and clinical evidence supports the concept of bidirectional microbiota-gut-brain interactions ( Mohajeri et al, 2018 ; Toribio-Mateas, 2018 ; Mohajeri, 2019 ), in which OMVs are active players ( Choi et al, 2019 ; Ladinsky et al, 2019 ). In this context, the maintenance of healthy gut microbiota during the interplanetary journeys, e.g., to Mars, will be a challenge in the near future.…”