Abstract
Purpose: :
Rapidly growing evidence suggests that neuroinflammation may contribute to degenerative diseases of the nervous system, including the eye. Furthermore, chronic low-grade inflammation of the mucosal membranes may generate or aggravate neuroinflammation. Probiotics are widely recommended to restore microbiota-host symbiosis on mucous membranes and for treating inflammatory diseases of the gut, airways and vagina. Recently, several studies suggested that killed probiotics (lysate) may also have immunomodulatory effects, but their effects on neuroinflammation have not yet been studied. Herewe present our first results on the effects of probiotics lysate on reducing release of pro-inflammatory cytokines from LPS stimulated macrophages in vitro, and on attenuating LPS-induced neuroinflammation in vivo. Our theory is that fragmentation may further enhance bioavailability and efficacy of probiotic lysate.
Methods: :
Tyndallized probiotics were prepared from industrially grown Lactobacillus acidophilus and Bifidobacterium longum by heat treatment for 1 h at 70°C on three consecutive days. Using ultrasonic fragmentation we prepared nano-size particles from probiotic lysate up to size less than 5.000nm. The influence of nano-size probiotics on TNFalpha and IL-1beta release were studied in vitro and in vivo.
Results: :
Anti-inflammatory effects of nano-size probiotics were tested in three different models: (i) In vitro: Lysate of Lactobacillus acidophilus and Bifidobacterium longum dose and size-dependently reduced pro-inflammatory cytokine release of LPS stimulated peritoneal macrophages of mouse, being the most effective the 1000 nanometer compared to the higher size. (ii) In vivo: Activation of microglia in brain and the retina was attenuated by nano-size probiotics in animal model of sublethal sepsis and of inflammatory bowel disease. (iii) Case reports: Brain damage improved up to 2 years after ischemic stroke and traumatic brain injury treated with a composition of nano-size probiotics, cod liver oil and vitamin B complex.
Conclusions: :
Taking together these findings from our and other laboratories, we may conclude that nano-size particles of probiotic (i) may have anti-inflammatory effect in vitro and in vivo, (ii) may be formulated with other active and synergistic compounds, and finally (iii) administration of nano-size probiotics may open a new approach for preventing and treating neuroinflammation and related diseases of the nervous system and the eye. Ongoing clinical trials are destined to confirm this hypothesis.
Keywords: inflammation • neuroprotection • nutritional factors