Lactobacillus reuteri-Specific Immunoregulatory Gene
            <i>rsiR</i>
            Modulates Histamine Production and Immunomodulation by Lactobacillus reuteri

Hemarajata, Peera; Gao, Chunying; Pflughoeft, Kathryn J.; Thomas, Carissa M.; Saulnier, Delphine M.; Spinler, Jennifer K.; Versalovic, James

doi:10.1128/jb.00261-13

Cited by 55 publications

(57 citation statements)

References 59 publications

(77 reference statements)

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“…This is an important finding, since several strains of L. reuteri have been shown to reduce colonic inflammation131846474849, but mechanisms by which this occurs are not completely known. Several strains of L. reuteri have been shown to reduce cytokine and chemokine production by monocytes, as well as epithelial cells1318, thus it is more likely that probiotic L. reuteri attenuates pathogen-induced colitis through direct effects on mucosal immune responses rather than mediating an effect through the microbiota.…”

Section: Discussionmentioning

confidence: 93%

Stressor exposure has prolonged effects on colonic microbial community structure in Citrobacter rodentium-challenged mice

Galley

Mackos

Varaljay

et al. 2017

Sci Rep

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Stressor exposure significantly affects the colonic mucosa-associated microbiota, and exacerbates Citrobacter rodentium-induced inflammation, effects that can be attenuated with probiotic Lactobacillus reuteri. This study assessed the structure of the colonic mucosa-associated microbiota in mice exposed to a social stressor (called social disruption), as well as non-stressed control mice, during challenge with the colonic pathogen C. rodentium. Mice were exposed to the social stressor or home cage control conditions for six consecutive days and all mice were challenged with C. rodentium immediately following the first exposure to the stressor. In addition, mice received probiotic L. reuteri, or vehicle as a control, via oral gavage following each stressor exposure. The stressor-exposed mice had significant differences in microbial community composition compared to non-stressed control mice. This difference was first evident following the six-cycle exposure to the stressor, on Day 6 post-C. rodentium challenge, and persisted for up to 19 days after stressor termination. Mice exposed to the stressor had different microbial community composition regardless of whether they were treated with L. reuteri or treated with vehicle as a control. These data indicate that stressor exposure affects the colonic microbiota during challenge with C. rodentium, and that these effects are long-lasting and not attenuated by probiotic L. reuteri.

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Section: Discussionmentioning

confidence: 93%

Stressor exposure has prolonged effects on colonic microbial community structure in Citrobacter rodentium-challenged mice

Galley

Mackos

Varaljay

et al. 2017

Sci Rep

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“…Mechanisms such as activation of c-Jun and the transcription factor AP-1 [41] and the ability to convert Lhistidine into the immunoregulatory signal histamine [42] are of importance for the anti-inflammatory effects of L. reuteri 6475. Furthermore, the genes cyclopropane fatty acid synthase (cfa) [43] and L. reuteri-specific immunoregulatory (rsiR) gene [44] have been implicated in the anti-inflammatory properties of L. reuteri 6475. In addition to these immunomodulatory properties in vitro, L. reuteri 6475 has also shown promising effects in animal studies [45][46][47].…”

Section: Immunomodulatory Effects Of Selected Lactic Acid Bacteriamentioning

confidence: 99%

Immunomodulation of Monocytes by Probiotic and Selected Lactic Acid Bacteria

Jensen

Drømtorp

Axelsson

et al. 2014

Probiotics & Antimicro. Prot.

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Some lactic acid bacteria (LAB), especially bacteria belonging to the genus Lactobacillus, are recognized as common inhabitants of the human gastrointestinal tract and have received considerable attention in the last decades due to their postulated health-promoting effects. LAB and probiotic bacteria can modulate the host immune response. However, much is unknown about the mediators and mechanisms responsible for their immunological effect. Here, we present a study using cytokine secretion from the monocytic cell line THP-1 and NF-κB activation in the monocytic cell line U937-3xkB-LUC to elucidate immune stimulating abilities of LAB in vitro. In this study, we investigate both commercially available and potential probiotic LAB strains, and the role of putative surface proteins of L. reuteri using mutants. L. reuteri strains induced the highest cytokine secretion and the highest NF-κB activation, whereas L. plantarum strains and L. rhamnosus GG were low inducers/activators. One of the putative L. reuteri surface proteins, Hmpref0536_10802, appeared to be of importance for the stimulation of THP-1 cells and the activation of NF-κB in U937-3xkB-LUC cells. Live and UV-inactivated preparations resulted in different responses for two of the strains investigated. Our results add to the complexity in the interaction between LAB and human cells and suggest the possible involvement of secreted pro- and anti-inflammatory mediators of LAB. It is likely that it is the sum of bacterial surface proteins and bacterial metabolites and/or secreted proteins that induce cytokine secretion in THP-1 cells and activate NF-κB in U937-3xkB-LUC cells in this study.

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“…This excessive inflammatory response is associated with immunopathology in the colon, and is consistent with clinical studies indicating that the symptoms of colonic diseases, such as the inflammatory bowel diseases, tend to be more severe during stressful periods. Because the prolonged restraint stressor and the SDR stressor reduce lactobacilli levels in the colon (Galley et al, 2014a; Galley et al, 2014b), and because lactobacilli are well-known to be immunomodulatory (Hemarajata et al, 2013; Jones and Versalovic, 2009; Lin et al, 2008; Pena et al, 2005; Thomas et al, 2012), we hypothesized that stressor-induced reductions in lactobacilli were contributing to changes in the mucosal immune response. This led to a series of experiments in which mice were given probiotic lactobacilli to determine whether increasing Lactobacillus levels in the intestines would prevent the deleterious effects of the stressor on colonic inflammation.…”

Section: Detrimental Effects Of the Microbiota On Host Immunity Durinmentioning

confidence: 99%

The role of the commensal microbiota in adaptive and maladaptive stressor-induced immunomodulation

Mackos

Maltz

Bailey

2017

Hormones and Behavior

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Over the past decade, it has become increasingly evident that there are extensive bidirectional interactions between the body and its microbiota. These interactions are evident during stressful periods, where it is recognized that commensal microbiota community structure is significantly changed. Many different stressors, ranging from early life stressors to stressors administered during adulthood, lead to significant, community-wide differences in the microbiota. The mechanisms through which this occurs are not yet known, but it is known that commensal microbes can recognize, and respond to, mammalian hormones and neurotransmitters, including those that are involved with the physiological response to stressful stimuli. In addition, the physiological stress response also changes many aspects of gastrointestinal physiology that can impact microbial community composition. Thus, there are many routes through which microbial community composition might be disrupted during stressful periods. The implications of these disruptions in commensal microbial communities for host health are still not well understood, but the commensal microbiota have been linked to stressor-induced immunopotentiation. The role of the microbiota in stressor-induced immunopotentiation can be adaptive, such as when these microbes stimulate innate defenses against bacterial infection. However, the commensal microbiota can also lead to maladaptive immune responses during stressor-exposure. This is evident in animal models of colonic inflammation where stressor exposure increases the inflammation through mechanisms involving the microbiota. It is likely that during stressor exposure, immune cell functioning is regulated by combined effects of both neurotransmitters/hormones and commensal microbes. Defining this regulation should be a focus of future studies.

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Lactobacillus reuteri-Specific Immunoregulatory Gene rsiR Modulates Histamine Production and Immunomodulation by Lactobacillus reuteri

Cited by 55 publications

References 59 publications

Stressor exposure has prolonged effects on colonic microbial community structure in Citrobacter rodentium-challenged mice

Stressor exposure has prolonged effects on colonic microbial community structure in Citrobacter rodentium-challenged mice

Immunomodulation of Monocytes by Probiotic and Selected Lactic Acid Bacteria

The role of the commensal microbiota in adaptive and maladaptive stressor-induced immunomodulation

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