Abstract
Lactobacillus johnsonii N6.2 mitigates the onset of type 1 diabetes (T1D) in biobreeding diabetes-prone rats, in part, through changes in kynurenine:tryptophan (K:T) ratios. The goal of this pilot study was to determine the safety, tolerance, and general immunological response of L. johnsonii N6.2 in healthy subjects. A double-blind, randomized clinical trial in 42 healthy individuals with no known risk factors for T1D was undertaken to evaluate subject responses to the consumption of L. johnsonii N6.2. Participants received 1 capsule/day containing 108 colony-forming units of L. johnsonii N6.2 or placebo for 8 weeks. Comprehensive metabolic panel (CMP), leukocyte subpopulations by complete blood count (CBC) and flow cytometry, serum cytokines, and relevant metabolites in the indoleamine-2,3-dioxygenase pathway were assessed. L. johnsonii N6.2 survival and intestinal microbiota was analyzed. Daily and weekly questionnaires were assessed for potential effects of probiotic treatment on general wellness. The administration of L. johnsonii N6.2 did not modify the CMP or CBC of participants suggesting general safety. In fact, L. johnsonii N6.2 administration significantly decreased the occurrence of abdominal pain, indigestion, and cephalic syndromes. As predicted, increased serum tryptophan levels increased resulting in a decreased K:T ratio was observed in the L. johnsonii N6.2 group. Interestingly, immunophenotyping assays revealed that monocytes and natural killer cell numbers were increased significantly after washout (12 weeks). Moreover, an increase of circulating effector Th1 cells (CD45RO+CD183+CD196−) and cytotoxic CD8+ T cells subset was observed in the L. johnsonii N6.2 group. Consumption of L. johnsonii N6.2 is well tolerated in adult control subjects, demonstrates systemic impacts on innate and adaptive immune populations, and results in a decreased K:T ratio. These data provide support for the safety and feasibility of using L. johnsonii N6.2 in prevention trials in subjects at risk for T1D.Trial registration: This trial was registered at http://clinicaltrials.gov as NCT02349360.
Highlights
Commensal bacteria regulate a myriad of host processes and provide several nutrients to their host as well as their symbionts within the microbial community [1, 2]
No alterations in the circulating levels of insulin and C-reactive protein (CRP) were observed in the L. johnsonii N6.2 group at 8 weeks or 12 weeks compared to placebo
We previously reported that the administration of L. johnsonii N6.2 to BB-DP rats resulted in decreased expression of IDO and, changes in the kynurenine:tryptophan (K:T) ratios in peripheral serum [25]
Summary
Commensal bacteria regulate a myriad of host processes and provide several nutrients to their host as well as their symbionts within the microbial community [1, 2] In healthy individuals, these relationships are thought to occur in equilibrium [3]. Recent studies have looked at the fluctuations in the microbiota and the rate of diabetes development in infant cohorts. These studies have shown a low abundance of lactate-producing and butyrate-producing species and an increase of the Bacteroides genus in children with autoimmunity when compared to controls [10, 11]. Kostic et al [12] further showed that the fluctuations in the microbiota composition occur prior to the onset of disease but after seroconversion
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