Our study shows the bidirectional relationship between the intestine-brain axis and the role of different probiotic strains in the presence of inflammatory insult, improving anxiety-like behavior, reducing inflammation, oxidative stress and tissue damage.
Bidirectional communication between brain and gut has long been recognized. There is a growing body of evidence documenting the ability of prebiotics, probiotics, synbiotics and other diets to normalize dysbiosis associated with psychological disorders [22, 23]. Numerous works focus on the impact of the microbiota on behaviors such as anxiety or depression [24, 25, 26]. Anxiety and depressive episodes are associated with dysregulation of the HPA axis [27]. Evidence from experiments carried out in animals with altered intestinal microbiota, whether GF mice or conventionally animals treated with antibiotics and/or probiotics or infected, all indicate that rodent behavioral responses are impacted when the bacterial status of the gut is manipulated [28, 29, 30].
Probiotics play a key role in the balance of the gut flora, restoring the composition of the microbiota [31]. Our results indicate immunomodulatory activity by probiotics, since they were able to reduce the inflammatory response through the reduction of different proinflammatory players (See Graphical abstract). LPS produced by Gram negatives bacteria enters in the circulation through intestinal permeability, activating the immune response and TLR4/NF-kB signaling pathway [32].
This result contributes to the gut-brain axis relationship. Some studies suggest that an improvement in the symptoms associated to psychiatric and neurological disorders, as well as the oxidative stress, inflammatory biomarkers and metabolic state in general, through the probiotic effects on CNS bidirectional circuits are mediated by the gut-microbiota-brain axis [33, 34]. Different probiotics have been investigated for psychiatric and neurological disorders; however, Bifidobacterium and Lactobacillus have been shown to be more effective [35]. Literature evidence shows that increased inflammation is associated with anxiety-like behavior [28–30, 36–38]. In general, the mechanisms underlying the effects of the microbiota on the CNS are multifactorial (immunologic, endocrine and neural), but these effects are believed to principally occur via the generation of bacterial metabolites [39]. The mechanisms of action of probiotics involve colonization of intestinal microbial; competitive exclusion of pathogens and bacteriocin production; modulation of enzymatic activities and production of volatile fatty acids. In addition, probiotics increase mucin production and cell adhesion in the gut [40]. Thus, probiotic metabolites are able to interact with the brain-gut axis and play a role in behavior [40].
The decrease in oxidative stress in animals supplemented with probiotics indicates immunomodulatory and antioxidant activity provided by probiotic supplementation. Thus, probiotics provide health benefits, mainly by maintaining intestinal integrity. This assertion can be supported by the results obtained in this study, the reduction of inflammation and oxidative stress, the preservation of intestinal villi, the better behavioral response as well as the reduction of brain inflammation confirm the interaction between the gut-brain bidirectional axis, demonstrating how the maintenance of intestinal integrity provided by probiotic microorganisms prevented inflammation in brain tissue, ensuring greater health and homeostasis.