Lactobacillus johnsonii N6.2 diminishes caspase-1 maturation in the gastrointestinal system of diabetes prone rats

Abstract

The cells of the gastrointestinal (GI) epithelium are the first to contact the microbiota and food components. As a direct consequence of this, these cells are the first line of defence and key players in priming the immune response. One of the first responses against GI insults is the formation of the inflammasome, a multiprotein complex assembled in response to environmental threats. The formation of the inflammasome regulates caspase-1 by cleaving it into its active form. Once activated, caspase-1 can cleave interleukin-1β (IL-1β), which promotes adaptive and humoral immunity. Some strains, like Lactobacillus johnsonii N6.2, are able to modulate the biosynthesis of important host metabolites mediating inflammation. Of these metabolites are the pro-inflammatory kynurenines. L. johnsonii N6.2 is able to downregulate kynurenines biosynthesis via a redox active mechanism negatively affecting indoleamine 2,3-dioxygenase activity. In this study, we evaluated the effects of L. johnsonii N6.2 combined with the natural antioxidant and anti-inflammatory molecule rosmarinic acid (RA). Inflammasome assembly and the kynurenine pathway were evaluated in GI samples of BioBreeding diabetes-prone (BB-DP) rats. In this work, BB-DP rats were fed daily with RA, L. johnsonii N6.2; or both combined. The transcriptional rate and proteins levels of inflammasome and kynurenine pathway components in ileum tissue were evaluated. Elevated levels of pro-caspase-1 were observed in rats fed with L. johnsonii, while RA had no effect on pro-caspase-1 expression. Western blot assays demonstrated that L. johnsonii fed rats showed lower levels of mature caspase-1, when compared to the other treatments. Furthermore, IL-1β maturation followed a similar pattern across the treatments. Differences were also observed between treatments in expression levels of key enzymes in the kynurenine pathway. These findings support the role of L. johnsonii in modulating the assembly of the inflammasome as well as some steps of the pro-inflammatory kynurenine pathway.

Oral Administration of a Select Mixture of Lactobacillus and Bacillus Alleviates Inflammation and Maintains Mucosal Barrier Integrity in the Ileum of Pigs Challenged with Salmonella Infantis

“…Previous studies indicate that Salmonella activates the NLRP3 and NLRC4 inflammasome, resulting in caspase-1 activation and rapid cell death [31,32]. There was evidence that L. johnsonii N6.2 suppressed the inflammasome and caspase-1 maturation lowering overall gastro-intestinal inflammation [33]. In our study, increased maturation of caspase-1 was observed in the SI but not in the PS piglets.…”

Insights from Bacteroides Species in Children with Type 1 Diabetes

“…Several studies have reported the beneficial role of different Lactobacillus species on delaying the development of T1D or reducing its complications, using mice models [ 83 , 84 , 85 , 86 ]. In the current study the fecal samples of T1D children showed lower numbers of Lactobacillus spp.…”

Lactobacillus johnsonii N6.2 and Blueberry Phytophenols Affect Lipidome and Gut Microbiota Composition of Rats Under High-Fat Diet

“…We have recorded several positive effects on animal models and successfully reproduced them in human subjects (22-27, 30, 32). Significant effects in lowering GI inflammation and boosting the immunological system were successfully demonstrated (27,30,67). Still, the biological molecules mediating such systemic effects has not yet been identified.…”

“…Additional evidence suggested that the benefits linked to the consumption of L. johnsonii N6.2 may begin with the prevention of early GI inflammatory processes. The data collected in this work demonstrate that BioBreeding Diabetes Prone (BB-DP) rats treated with L. johnsonii N6.2 exhibit lower levels of the active fraction of caspase-1 in ileum tissue, suggesting that L. johnsonii N6.2 can reduce inflammatory processes by decreasing the activation of the inflammasome ( 27 ). The inflammasome can be modulated by the presence of specific fatty acids (FAs), which have been described as one of the main regulators of metabolism, cellular signaling and immunity ( 28 , 29 ).…”