Amelioration of regulatory T cells by Lactobacillus delbrueckii and Lactobacillus rhamnosus in pristane‐induced lupus mice model

Abstract

Regulatory T cells (Tregs) play an indispensable role in the control of immune responses and induction of peripheral tolerance. Dysregulation of Tregs is involved in the pathogenesis of systemic lupus erythematosus (SLE). Tolerogenic probiotics have shown beneficial effects in the control of autoimmune diseases. We evaluated the prophylactic and therapeutic effects of Lactobacillus delbrueckii and Lactobacillus rhamnosus on Tregs and their related molecules in pristane‐induced lupus mice model. Fifty‐four female BALB/c mice (3–5 weeks) were randomly divided into nine groups. Lupus was induced in all groups using pristane. Prophylactic groups were treated from Day 0 (at the time of pristane injection) and treatment groups were treated 2 months later with L. rhamnosus, L. delbrueckii, mix of both probiotics, and prednisolone. One group was considered as SLE‐induced control group without any treatment. Presence of antinuclear antibodies (ANA), antidouble‐stranded DNA (anti‐dsDNA), antiribonucleoprotein (anti‐RNP), proteinuria, and serum level of creatinine, urea, the expression of forkhead box P3 (Foxp3), interleukin 6 (IL‐6), IL‐10, transforming growth factor β, and the number of Tregs were determined. SLE induction by pristane led to the formation of lipogranuloma, presence of ANA, anti‐dsDNA, and anti‐RNP. Probiotics consumption decreased the level of lipogranuloma, ANA, and anti‐dsDNA. In addition, in probiotics receiving groups, Tregs and the expression level of Foxp3 increased, while IL‐6 decreased. The effect of probiotics in the prophylactic group was more prominent. The results may indicate the effectiveness of L. delbrueckii and L. rhamnosus in the enhancement of Tregs and the decrease of inflammatory cytokines and disease severity in SLE‐induced mice.

Alterations of the Gut Microbiota Associated With Promoting Efficacy of Prednisone by Bromofuranone in MRL/lpr Mice

“…Meanwhile, the combined use of bromofuranone and prednisone induced the other alterations in Lactobacillus , Allobaculum , Sutterella , and Adlercreutzia , which were not induced by prednisone alone. It was reported that Lactobacillus was beneficial to relieve lupus activity (Mu et al, 2017) by suppressing proinflammatory responses and increasing the number of inducible regulatory T cells (Mohamadzadeh et al, 2011; Khorasani et al, 2018). Moreover, three other specifically altered genera, Allobaculum , Sutterella , and Adlercreutzia , were negatively correlated with lupus activity and were all reported to be capable of immunoregulatory in intestines (Hiippala et al, 2016; Calvo-Barreiro et al, 2018; Scott et al, 2018).…”

Aberrant Gut Microbiome Contributes to Intestinal Oxidative Stress, Barrier Dysfunction, Inflammation and Systemic Autoimmune Responses in MRL/lpr Mice

“…Intestinal microbiome dysbiosis is associated with chronic low-grade inflammation, and also triggers autoreactive T cells (CD4+ and CD8+ T cells) to drive spontaneous autoimmunity in target organs (18)(19)(20). The intestinal commensals interact with the host mucosal immune system leading to an imbalance in Treg and Th17 cells (21). Moreover, recent evidence suggests that fecal microbiome transplantation or probiotic supplementation could have beneficial effects in ADs based on evidence from both animal models and human studies (22)(23)(24)(25)(26)(27)(28).…”

Benefits of Probiotics in Rheumatic Diseases

“…Despite the lack of clinical evidences, some experimental studies are encouraging. Using mouse models of SLE some authors have demonstrated that probiotic supplementation ameliorates disease activity, Treg regulation, and typical comorbidities occurring in SLE including cardiovascular complications (27,28). More recently, lactobacilli administration appeared to delay SLE progression via mechanisms involving Treg induction and IL-10 production (29).…”