Enriched environment causes epigenetic changes in hippocampus and improves long-term cognitive function in sepsis.

Sepsis is defined as a life-threatening organ dysfunction caused by an inappropriate host response to infection. The presence of oxidative stress and inflammatory mediators in sepsis leads to dysregulated gene expression, leading to a hyperinflammatory response. Environmental conditions play an important role in various pathologies depending on the stimulus it presents. A standard environment condition (SE) may offer reduced sensory and cognitive stimulation, but an enriched environment improves spatial learning, prevents cognitive deficits induced by disease stress, and is an important modulator of epigenetic enzymes. The study evaluated the epigenetic alterations and the effects of the environmental enrichment (EE) protocol in the brain of animals submitted to sepsis by cecal ligation and perforation (CLP). Male Wistar rats were divided into sham and CLP at 24 h, 72 h, 10 days and 30 days after sepsis. Other male Wistar rats were distributed in a SE or in EE for forty-five days. Behavioral tests, analysis of epigenetic enzymes:histone acetylase (HAT), histone deacetylase (HDAC) and DNA methyltransferase (DNMT), biochemical and synaptic plasticity analyzes were performed. An increase in HDAC and DNMT activities was observed at 72 h, 10 days and 30 days. There was a positive correlation between epigenetic enzymes DNMT and HDAC 24 h, 10 days and 30 days. After EE, HDAC and DNMT enzyme activity decreased, cognitive impairment was reversed, IL1-ß levels decreased and there was an increase in PSD-95 levels in the hippocampus. Interventions in environmental conditions can modulate the outcomes of long-term cognitive consequences associated with sepsis, supporting the idea of the potential benefits of EE.

Effects of different probiotic strains B. lactis, L. rhamnosus and L. reuteri on brain-intestinal axis immunomodulation in an endotoxin-induced inflammation.

The study evaluated the effects of supplementation with three different probiotic strains Bifidobacterium lactis (LACT GB™), Lactobacillus rhamnosus (RHAM GB™) and Lactobacillus reuteri (REUT GB™) on brain-intestinal immunomodulation in an animal model of LPS-induced inflammation. Fifty mice Balb/C were distributed into five groups: control; lipopolysaccharide (LPS); LPS + B. lactis (LACT GB™); LPS + L. rhamnosus (RHAM GB™); and LPS + L. reuteri (REUT GB™). The animals were supplemented with their respective probiotic microorganisms daily, for 30 days, at a concentration of 1 × 109 CFU/animal/day. After 30 days of supplementation, animals received the inflammatory insult by LPS (15 mg/kg). Behavioral tests, oxidative stress and inflammation were performed, as well as gut and brain histology. In the behavioral test, LPS + B. lactis group was less anxious than the other groups. Serum interleukin IL-1ß and IL-6 levels increased in all groups that received the LPS insult, and there was a reduction in inflammation in the supplemented groups when compared to the LPS group in brain and gut. There is a reduction in myeloperoxidase activity and oxidative stress in groups supplemented with probiotics. In intestine histological analysis occurs damage to the tissue integrity in the LPS group, in the other hand, occurs preservation of integrity in the probiotic supplemented animals. In the brain, infiltrates of perivascular inflammatory cells can be seen in the LPS group. The three probiotic studies showed efficient immunomodulating activity and ensured integrity of the intestinal barrier function, even after the severe insult by LPS. These results show the important role of probiotics in the gut-brain axis. Graphical abstract illustratively represents the gut-brain axis and how different probiotic strains influence the immunomodulatory response releasing different pro- and anti-inflammatory cytokines, and their role in the balance of dysbiosis.